17-46929561-C-T

Position:

chr17-46929561-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004287.5(GOSR2):c.71C>T(p.Thr24Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,557,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

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:

ENSG00000262633 (HGNC:):

ENSG00000262633 links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16815332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOSR2	NM_004287.5 linkuse as main transcript	c.71C>T	p.Thr24Met	missense_variant	2/6	ENST00000640051.2	NP_004278.2	O14653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2 linkuse as main transcript	c.71C>T	p.Thr24Met	missense_variant	2/6	1	NM_004287.5	ENSP00000492751.1		O14653-1
ENSG00000262633	ENST00000571841.1 linkuse as main transcript	n.71C>T		non_coding_transcript_exon_variant	2/10	5		ENSP00000461460.1		E7EQ34

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251196

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135780

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1405682

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

702690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000113

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000606

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Progressive myoclonic epilepsy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2022

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 24 of the GOSR2 protein (p.Thr24Met). This variant is present in population databases (rs528931142, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with GOSR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 568150). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.0094

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

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.033

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.89

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

M_CAP

Benign

0.014

MetaRNN

Benign

0.17

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;.;.;L;.;.;L;.;L;.;.;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.5

.;.;.;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

REVEL

Benign

0.14

Sift

Benign

0.21

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

Sift4G

Benign

0.13

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

Polyphen

0.58, 0.45

.;.;.;P;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.58, 0.60, 0.53, 0.65

MutPred

0.22

Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);.;Loss of phosphorylation at T24 (P = 0.0543);.;.;.;Loss of phosphorylation at T24 (P = 0.0543);Loss of phosphorylation at T24 (P = 0.0543);.;.;.;.;.;

MVP

0.53

MPC

0.23

ClinPred

0.24

GERP RS

3.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.072

gMVP

0.21

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