chr17-46923197-A-T

Variant names:

• chr17-46923197-A-T
• rs1413496484
• NM_004287.5:c.5A>T

Variant summary

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

The NM_004287.5(GOSR2):​c.5A>T​(p.Asp2Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000043 in 1,395,214 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: 0.0000043 (0 hom.)
• Consequence: GOSR2 NM_004287.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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]

ENSG00000262633 (HGNC:):

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]

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

ACMG classification

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	c.5A>T	p.Asp2Val	missense_variant	Exon 1 of 6	ENST00000640051.2	NP_004278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2	c.5A>T	p.Asp2Val	missense_variant	Exon 1 of 6	1	NM_004287.5	ENSP00000492751.1
ENSG00000262633	ENST00000571841.1	n.5A>T		non_coding_transcript_exon_variant	Exon 1 of 10	5		ENSP00000461460.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000648 AC: 1 AN: 154370 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81650

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000169

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000430 AC: 6 AN: 1395214 Hom.: 0 Cov.: 30 AF XY: 0.00000436 AC XY: 3 AN XY: 688460

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000558

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	0.0040	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;.;.;.;.;.;T;.;.;.;.;.;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.39	T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.81	.;.;.;L;.;.;L;.;L;.;.;.;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-4.2	.;.;.;D;D;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.26
Sift	Uncertain	0.0010	.;.;.;D;D;.;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.0020	.;.;.;D;D;D;.;.;.;.;D;.;.;.
Polyphen		0.81, 0.50	.;.;.;P;.;.;P;.;.;.;.;.;.;.
Vest4		0.45, 0.47, 0.39, 0.48
MutPred		0.55		Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);Loss of disorder (P = 0.0823);
MVP		0.79
MPC		0.64
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.67
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1413496484; hg19: chr17-45000563;