rs749270151

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_004287.5(GOSR2):c.17A>G(p.Gln6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,550,018 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 4 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.96

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01972729).

BP6

Variant 17-46923209-A-G is Benign according to our data. Variant chr17-46923209-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 462913.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000123 (172/1397782) while in subpopulation SAS AF= 0.00211 (167/79210). AF 95% confidence interval is 0.00185. There are 4 homozygotes in gnomad4_exome. There are 133 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOSR2	NM_004287.5 linkuse as main transcript	c.17A>G	p.Gln6Arg	missense_variant	1/6	ENST00000640051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOSR2	ENST00000640051.2 linkuse as main transcript	c.17A>G	p.Gln6Arg	missense_variant	1/6	1	NM_004287.5	P3	O14653-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000363

AC:

AN:

154194

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

81558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00246

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

172

AN:

1397782

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

133

AN XY:

689528

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.000630

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 06, 2018

The p.Q6R variant (also known as c.17A>G), located in coding exon 1 of the GOSR2 gene, results from an A to G substitution at nucleotide position 17. The glutamine at codon 6 is replaced by arginine, an amino acid with highly similar properties. Based on data from gnomAD, the G allele has an overall frequency of approximately 0.038% (56/147100) total alleles studied. The highest observed frequency was 0.24% (55/22820) of South Asian alleles.This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Progressive myoclonic epilepsy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Benign

-0.084

Eigen_PC

Benign

0.082

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.0077

MetaRNN

Benign

0.020

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.75

N;N;N;N;N;N

PrimateAI

Uncertain

0.57

Polyphen

0.017, 0.0050

.;.;.;B;.;.;B;.;.;.;.;.;.;.

Vest4

0.29, 0.28, 0.21, 0.28

MutPred

0.38

Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);Gain of MoRF binding (P = 0.0084);

MVP

0.45

MPC

0.20

ClinPred

0.12

GERP RS

5.0

Varity_R

0.34

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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