rs145397970

Positions:

chr6-2948334-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_004568.6(SERPINB6):c.1095C>T(p.Asn365=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,614,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

SERPINB6
NM_004568.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -7.36

Variant links:

Genes affected

SERPINB6 (HGNC:8950): (serpin family B member 6) The protein encoded by this gene is a member of the serpin (serine proteinase inhibitor) superfamily, and ovalbumin(ov)-serpin subfamily. It was originally discovered as a placental thrombin inhibitor. The mouse homolog was found to be expressed in the hair cells of the inner ear. Mutations in this gene are associated with nonsyndromic progressive hearing loss, suggesting that this serpin plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]

SERPINB6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-2948334-G-A is Benign according to our data. Variant chr6-2948334-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 165188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-2948334-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-7.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPINB6	NM_004568.6 linkuse as main transcript	c.1095C>T	p.Asn365=	synonymous_variant	7/7	ENST00000380539.7	NP_004559.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPINB6	ENST00000380539.7 linkuse as main transcript	c.1095C>T	p.Asn365=	synonymous_variant	7/7	3	NM_004568.6	ENSP00000369912	P1

Frequencies

GnomAD3 genomes

AF:

0.000966

AC:

147

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00135

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00142

AC:

357

AN:

251292

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00420

Gnomad NFE exome

AF:

0.00219

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00160

AC:

2344

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1099

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00461

Gnomad4 NFE exome

AF:

0.00180

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000965

AC:

147

AN:

152298

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00135

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000703

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 11, 2015

p.Asn365Asn in Exon 08 of SERPINB6: This variant is not expected to have clinica l significance because it does not alter an amino acid residue, is not located w ithin the splice consensus sequence, and has been identified in 0.3% (23/5696) F innish chromosomes and in 0.2% (156/66564) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs145397970) . -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 06, 2023

- -

SERPINB6-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.18

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over