17-46929530-G-A

Position:

chr17-46929530-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004287.5(GOSR2):c.40G>A(p.Glu14Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000414 in 1,549,904 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 3 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 7.75

Variant links:

Genes affected

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

GOSR2 links:

LRRC37A2 (HGNC:):

LRRC37A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008037865).

BP6

Variant 17-46929530-G-A is Benign according to our data. Variant chr17-46929530-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 205627.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=4}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00214 (325/152220) while in subpopulation AFR AF= 0.00758 (315/41538). AF 95% confidence interval is 0.00689. There are 0 homozygotes in gnomad4. There are 149 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOSR2	NM_004287.5 linkuse as main transcript	c.40G>A	p.Glu14Lys	missense_variant	2/6	ENST00000640051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOSR2	ENST00000640051.2 linkuse as main transcript	c.40G>A	p.Glu14Lys	missense_variant	2/6	1	NM_004287.5	P3	O14653-1

Frequencies

GnomAD3 genomes

AF:

0.00213

AC:

324

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000514

AC:

129

AN:

251084

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.00708

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000226

AC:

316

AN:

1397684

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

125

AN XY:

699456

show subpopulations

Gnomad4 AFR exome

AF:

0.00782

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000106

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000114

Gnomad4 OTH exome

AF:

0.000584

GnomAD4 genome

AF:

0.00214

AC:

325

AN:

152220

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

149

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00758

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.00255

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000576

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 09, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Progressive myoclonic epilepsy

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 21, 2024	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

.;.;.;.;.;.;T;.;.;.;.;.;.;.;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.0080

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

.;.;.;M;.;.;M;.;M;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.0

.;.;.;D;D;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.20

Sift

Uncertain

0.0040

.;.;.;D;T;.;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.092

.;.;.;T;D;T;.;.;.;.;T;.;.;.;.

Polyphen

1.0, 0.97

.;.;.;D;.;.;D;.;.;.;.;.;.;.;.

Vest4

0.79, 0.77, 0.77, 0.75

MVP

0.51

MPC

0.25

ClinPred

0.068

GERP RS

4.8

Varity_R

0.58

gMVP

0.37

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