VCV000135239.31 - ClinVar

NM_014159.7(SETD2):c.4193T>C (p.Ile1398Thr)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

3 out of 4 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_014159.7(SETD2):c.4193T>C (p.Ile1398Thr)

Variation ID: 135239 Accession: VCV000135239.31

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p21.31 3: 47120443 (GRCh38) [ NCBI UCSC ] 3: 47161933 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 9, 2014	Mar 7, 2026	Sep 5, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_014159.7:c.4193T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_054878.5:p.Ile1398Thr	missense
NM_001349370.3:c.4061T>C	NP_001336299.1:p.Ile1354Thr	missense
NR_146158.3:n.4382T>C		non-coding transcript variant
NC_000003.12:g.47120443A>G
NC_000003.11:g.47161933A>G
NG_032091.1:g.48535T>C
LRG_775:g.48535T>C
LRG_775t1:c.4193T>C	LRG_775p1:p.Ile1398Thr

... more HGVS ... less HGVS

Protein change

I1398T, I1354T

Other names

Canonical SPDI

NC_000003.12:47120442:A:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00019

Exome Aggregation Consortium (ExAC) 0.00026

The Genome Aggregation Database (gnomAD) 0.00029

The Genome Aggregation Database (gnomAD) 0.00032

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00038

Trans-Omics for Precision Medicine (TOPMed) 0.00042

The Genome Aggregation Database (gnomAD), exomes 0.00048

Links

dbSNP: rs145732065 ClinGen: CA162110 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SETD2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1445	1484

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (2)	criteria provided, single submitter	Feb 1, 2024	RCV000122051.3
Luscan-Lumish syndrome	Benign (1)	criteria provided, single submitter	Sep 5, 2025	RCV000960671.10
not provided	Likely benign (1)	criteria provided, single submitter	Mar 1, 2023	RCV003436937.20

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
benign (Feb 01, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria)	not specified	Athena Diagnostics Accession: SCV005621142.1 First in ClinVar: Jan 19, 2025 Last updated: Jan 19, 2025	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Benign (Sep 05, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Luscan-Lumish syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001107680.7 First in ClinVar: Dec 17, 2019 Last updated: Mar 07, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Mar 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV004154377.20 First in ClinVar: Nov 20, 2023 Last updated: Jan 11, 2026	Comment: show SETD2: BP4, BS2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 2

not provided (Sep 19, 2013) N Not contributing to aggregate classification	no classification provided	AllHighlyPenetrant	ITMI Accession: SCV000086262.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 Observation: 7 Observation 1 Collection method: reference population Allele origin: germline Affected status: unknown Ethnicity/Population group: Whole_cohort Platform type: next-gen sequencing Platform name: Complete Genomics Observation 2 Collection method: reference population Allele origin: germline Affected status: unknown Ethnicity/Population group: African Platform type: next-gen sequencing Platform name: Complete Genomics Observation 3 Collection method: reference population Allele origin: germline Affected status: unknown Ethnicity/Population group: African_European Platform type: next-gen sequencing Platform name: Complete Genomics Observation 4 Collection method: reference population Allele origin: germline Affected status: unknown Ethnicity/Population group: Central_Asian Platform type: next-gen sequencing Platform name: Complete Genomics Observation 5 Collection method: reference population Allele origin: germline Affected status: unknown Ethnicity/Population group: East_Asian Platform type: next-gen sequencing Platform name: Complete Genomics Observation 6 Collection method: reference population Allele origin: germline Affected status: unknown Ethnicity/Population group: European Platform type: next-gen sequencing Platform name: Complete Genomics Observation 7 Collection method: reference population Allele origin: germline Affected status: unknown Ethnicity/Population group: Hispanic Platform Type: next-gen sequencing Platform Name: Complete Genomics

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs145732065 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Mar 08, 2026