17-46923199-C-G

Variant names:

• chr17-46923199-C-G
• rs12944167
• NM_004287.5:c.7C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363851.2(GOSR2):​c.-459C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,547,222 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: GOSR2 NM_001363851.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.947
• Publications: 6 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08525905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363851.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	NM_004287.5	MANE Select	c.7C>G	p.Pro3Ala	missense	Exon 1 of 6	NP_004278.2
	GOSR2	NM_001363851.2		c.-459C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001350780.1	A0A1W2PRL0
	GOSR2	NM_001321134.2		c.-96C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001308063.1	A0A1W2PQE0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.7C>G	p.Pro3Ala	missense	Exon 1 of 6	ENSP00000492751.1	O14653-1
	GOSR2	ENST00000225567.9	TSL:1	c.7C>G	p.Pro3Ala	missense	Exon 1 of 7	ENSP00000225567.4	O14653-2
	GOSR2	ENST00000640621.1	TSL:1	c.7C>G	p.Pro3Ala	missense	Exon 1 of 5	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000130 AC: 2 AN: 154338 AF XY: 0.0000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000887

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000108 AC: 15 AN: 1394986 Hom.: 0 Cov.: 30 AF XY: 0.0000131 AC XY: 9 AN XY: 688312

African (AFR) AF: 0.0000952 AC: 3 AN: 31518

American (AMR) AF: 0.00 AC: 0 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25126

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35708

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00000930 AC: 10 AN: 1075164

Other (OTH) AF: 0.00 AC: 0 AN: 57860

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74376

African (AFR) AF: 0.0000724 AC: 3 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 128

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Progressive myoclonic epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.2
DANN	Benign	0.73
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.14	N
PhyloP100		0.95
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.24
Sift	Benign	0.46	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.21		Loss of catalytic residue at P3 (P = 0.051)
MVP		0.66
MPC		0.16
ClinPred		0.057	T
GERP RS		4.0
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.093
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs12944167; hg19: chr17-45000565;