Genetic Variant GOSR1:c.-41C>A (chr17-30484216-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001007024.2(GOSR1):c.-41C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000897 in 1,571,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

GOSR1
NM_001007024.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Variant links:

Genes affected

GOSR1 (HGNC:4430): (golgi SNAP receptor complex member 1) This gene encodes a trafficking membrane protein which transports proteins among the endoplasmic reticulum and the Golgi and between Golgi compartments. This protein is considered an essential component of the Golgi SNAP receptor (SNARE) complex. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GOSR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32567012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOSR1	NM_001007025.2 link	c.149C>A	p.Ser50Tyr	missense_variant, splice_region_variant	Exon 3 of 9	ENST00000451249.7	NP_001007026.1	O95249E9PCW1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOSR1	ENST00000451249.7 link	c.149C>A	p.Ser50Tyr	missense_variant, splice_region_variant	Exon 3 of 9	2	NM_001007025.2	ENSP00000414441.2		E9PCW1

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.000108

AC:

AN:

251044

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000923

AC:

131

AN:

1419410

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

709052

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000102

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.155C>A (p.S52Y) alteration is located in exon 3 (coding exon 3) of the GOSR1 gene. This alteration results from a C to A substitution at nucleotide position 155, causing the serine (S) at amino acid position 52 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Uncertain

0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

T;.;.

Eigen

Benign

0.049

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D;T

M_CAP

Benign

0.0094

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-2.1

N;N;.

REVEL

Benign

0.18

Sift

Uncertain

0.029

D;D;.

Sift4G

Uncertain

0.058

T;D;T

Polyphen

0.15

B;B;.

Vest4

0.74

MVP

0.63

MPC

0.24

ClinPred

0.049

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.60

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