chr17-46931137-T-G

Variant names:

• chr17-46931137-T-G
• NM_004287.5:c.133T>G

Variant summary

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

The NM_004287.5(GOSR2):​c.133T>G​(p.Phe45Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,956 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GOSR2 NM_004287.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20

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]

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.133T>G	p.Phe45Val	missense_variant	Exon 3 of 6	ENST00000640051.2	NP_004278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOSR2	ENST00000640051.2	c.133T>G	p.Phe45Val	missense_variant	Exon 3 of 6	1	NM_004287.5	ENSP00000492751.1
ENSG00000262633	ENST00000571841.1	n.133T>G		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000461460.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458956 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 726050

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D;D;D;.;D;D;.;D;D;D;D;D;D;.;D;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	.;.;.;M;.;.;M;.;M;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.2	.;.;.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.20
Sift	Benign	0.50	.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.53	.;.;.;T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.
Polyphen		0.44, 0.31	.;.;.;B;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.75, 0.79
MutPred		0.45		Gain of disorder (P = 0.078);.;Gain of disorder (P = 0.078);Gain of disorder (P = 0.078);.;.;Gain of disorder (P = 0.078);Gain of disorder (P = 0.078);Gain of disorder (P = 0.078);.;.;Gain of disorder (P = 0.078);.;.;.;Gain of disorder (P = 0.078);.;.;.;.;.;.;.;
MVP		0.83
MPC		0.23
ClinPred		0.83	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-45008503; COSMIC: COSV99845939; COSMIC: COSV99845939;