Genetic Variant NM_004287.5:c.4G>T (chr17-46923196-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004287.5(GOSR2):c.4G>T(p.Asp2Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,394,942 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.75

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:

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:

GOSR2-DT (HGNC:55346): (GOSR2 divergent transcript)

GOSR2-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOSR2	NM_004287.5 link	c.4G>T	p.Asp2Tyr	missense_variant	Exon 1 of 6	ENST00000640051.2	NP_004278.2	O14653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2 link	c.4G>T	p.Asp2Tyr	missense_variant	Exon 1 of 6	1	NM_004287.5	ENSP00000492751.1		O14653-1
ENSG00000262633	ENST00000571841.1 link	n.4G>T		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000461460.1		E7EQ34

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

154336

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81640

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:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1394942

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

688318

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.30e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

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

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.36

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

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.65

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

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.81

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

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.2

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

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

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

Sift4G

Pathogenic

0.0010

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

Polyphen

0.96, 0.86

.;.;.;D;.;.;P;.;.;.;.;.;.;.

Vest4

0.44, 0.46, 0.40, 0.46

MutPred

0.57

Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);Loss of disorder (P = 0.0754);

MVP

0.80

MPC

0.71

ClinPred

0.99

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.71

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over