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NM_015443.4(KANSL1):c.1126A>G (p.Ile376Val) AND Koolen-de Vries syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 29, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001035154.6

Allele description [Variation Report for NM_015443.4(KANSL1):c.1126A>G (p.Ile376Val)]

NM_015443.4(KANSL1):c.1126A>G (p.Ile376Val)

Gene:
KANSL1:KAT8 regulatory NSL complex subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_015443.4(KANSL1):c.1126A>G (p.Ile376Val)
HGVS:
  • NC_000017.11:g.46171018T>C
  • NG_032784.1:g.59357A>G
  • NM_001193465.2:c.1126A>G
  • NM_001193466.2:c.1126A>G
  • NM_001379198.1:c.1126A>G
  • NM_015443.4:c.1126A>GMANE SELECT
  • NP_001180394.1:p.Ile376Val
  • NP_001180395.1:p.Ile376Val
  • NP_001366127.1:p.Ile376Val
  • NP_056258.1:p.Ile376Val
  • NC_000017.10:g.44248384T>C
  • NM_001193466.1:c.1126A>G
Protein change:
I376V
Links:
dbSNP: rs754713192
NCBI 1000 Genomes Browser:
rs754713192
Molecular consequence:
  • NM_001193465.2:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193466.2:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379198.1:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015443.4:c.1126A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Koolen-de Vries syndrome (KDVS)
Synonyms:
KANSL1-Related Intellectual Disability Syndrome
Identifiers:
MONDO: MONDO:0012496; MedGen: C1864871; Orphanet: 96169; OMIM: 610443

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001198469Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Mar 29, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001198469.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KANSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 379183). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces isoleucine with valine at codon 376 of the KANSL1 protein (p.Ile376Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024