NM_004568.6(SERPINB6):c.1096G>A (p.Gly366Arg) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 22, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002226024.7

Allele description [Variation Report for NM_004568.6(SERPINB6):c.1096G>A (p.Gly366Arg)]

NM_004568.6(SERPINB6):c.1096G>A (p.Gly366Arg)

Gene:

SERPINB6:serpin family B member 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p25.2

Genomic location:

Preferred name:

NM_004568.6(SERPINB6):c.1096G>A (p.Gly366Arg)

HGVS:

NC_000006.12:g.2948333C>T
NG_027692.1:g.28833G>A
NM_001195291.3:c.1108G>A
NM_001271822.2:c.1138G>A
NM_001271823.2:c.1153G>A
NM_001271824.2:c.1096G>A
NM_001271825.2:c.1096G>A
NM_001297699.2:c.1096G>A
NM_001297700.2:c.1096G>A
NM_001374515.1:c.1108G>A
NM_001374516.1:c.1096G>A
NM_001374517.1:c.964G>A
NM_004568.6:c.1096G>AMANE SELECT
NP_001182220.2:p.Gly370Arg
NP_001258751.1:p.Gly380Arg
NP_001258752.1:p.Gly385Arg
NP_001258753.1:p.Gly366Arg
NP_001258754.1:p.Gly366Arg
NP_001284628.1:p.Gly366Arg
NP_001284629.1:p.Gly366Arg
NP_001361444.1:p.Gly370Arg
NP_001361445.1:p.Gly366Arg
NP_001361446.1:p.Gly322Arg
NP_004559.4:p.Gly366Arg
NC_000006.11:g.2948567C>T
NM_004568.5:c.1096G>A
NR_164657.1:n.1145G>A

Protein change:

G322R

Links:

dbSNP: rs765798757

Molecular consequence:

NM_001195291.3:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271822.2:c.1138G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271823.2:c.1153G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271824.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001271825.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001297699.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001297700.2:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374515.1:c.1108G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374516.1:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374517.1:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004568.6:c.1096G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164657.1:n.1145G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002504005	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 22, 2025)	germline	clinical testing	Citation Link,
SCV003250660	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002504005

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 22, 2025)

germline

clinical testing

Citation Link,

SCV003250660

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 2, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV002504005.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis suggests that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003250660.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 366 of the SERPINB6 protein (p.Gly366Arg). This variant is present in population databases (rs765798757, gnomAD 0.01%). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1678710). This variant has not been reported in the literature in individuals affected with SERPINB6-related conditions.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 30, 2025

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