rs12944167

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004287.5(GOSR2):c.7C>A(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,546,906 control chromosomes in the GnomAD database, including 534 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.018 ( 45 hom., cov: 33)

Exomes 𝑓: 0.024 ( 489 hom. )

Consequence

GOSR2
NM_004287.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.947

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032203794).

BP6

Variant 17-46923199-C-A is Benign according to our data. Variant chr17-46923199-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0181 (2765/152350) while in subpopulation NFE AF = 0.0235 (1602/68044). AF 95% confidence interval is 0.0226. There are 45 homozygotes in GnomAd4. There are 1391 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOSR2	NM_004287.5 link	c.7C>A	p.Pro3Thr	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.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 6	1	NM_004287.5	ENSP00000492751.1		O14653-1
ENSG00000262633	ENST00000571841.1 link	n.7C>A		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000461460.1		E7EQ34

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2766

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0180

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0236

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0224

AC:

3462

AN:

154338

AF XY:

0.0237

show subpopulations

Gnomad AFR exome

AF:

0.00334

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0674

Gnomad EAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.0282

Gnomad NFE exome

AF:

0.0247

Gnomad OTH exome

AF:

0.0249

GnomAD4 exome

AF:

0.0235

AC:

32809

AN:

1394556

Hom.:

489

Cov.:

AF XY:

0.0238

AC XY:

16356

AN XY:

688094

show subpopulations

African (AFR)

AF:

0.00349

AC:

110

AN:

31516

American (AMR)

AF:

0.0125

AC:

447

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

1651

AN:

25122

East Asian (EAS)

AF:

0.00193

AC:

AN:

35708

South Asian (SAS)

AF:

0.0253

AC:

2005

AN:

79118

European-Finnish (FIN)

AF:

0.0289

AC:

1421

AN:

49126

Middle Eastern (MID)

AF:

0.0124

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.0240

AC:

25836

AN:

1074774

Other (OTH)

AF:

0.0207

AC:

1200

AN:

57842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

1401

2802

4202

5603

7004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1010

2020

3030

4040

5050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0181

AC:

2765

AN:

152350

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1391

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00433

AC:

180

AN:

41572

American (AMR)

AF:

0.0179

AC:

274

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0683

AC:

237

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5190

South Asian (SAS)

AF:

0.0224

AC:

108

AN:

4826

European-Finnish (FIN)

AF:

0.0301

AC:

320

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1602

AN:

68044

Other (OTH)

AF:

0.0114

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

142

284

427

569

711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0222

Hom.:

128

Bravo

AF:

0.0164

TwinsUK

AF:

0.0216

AC:

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.00345

AC:

ESP6500EA

AF:

0.0179

AC:

116

ExAC

AF:

0.0171

AC:

539

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Dec 01, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 07, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 03, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive myoclonic epilepsy

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 23, 2017

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0045

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

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.41

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

MetaRNN

Benign

0.0032

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.59

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

PhyloP100

0.95

PrimateAI

Uncertain

0.62

PROVEAN

Benign

1.1

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

REVEL

Benign

0.13

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.23, 0.22, 0.090, 0.23

MPC

0.19

ClinPred

0.0083

GERP RS

4.0

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.052

gMVP

0.10

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over