chr17-30484697-C-T

Variant names:

• chr17-30484697-C-T
• rs369366770
• NM_001007025.2:c.269C>T

Variant summary

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

The NM_001007025.2(GOSR1):​c.269C>T​(p.Thr90Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,574,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: GOSR1 NM_001007025.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61
• Publications: 1 publications found

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]

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=0.1338942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007025.2. 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
	GOSR1	NM_001007025.2	MANE Select	c.269C>T	p.Thr90Ile	missense	Exon 4 of 9	NP_001007026.1	E9PCW1
	GOSR1	NM_004871.3		c.275C>T	p.Thr92Ile	missense	Exon 4 of 9	NP_004862.1	O95249-1
	GOSR1	NM_001007024.2		c.80C>T	p.Thr27Ile	missense	Exon 4 of 9	NP_001007025.1	O95249-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR1	ENST00000451249.7	TSL:2 MANE Select	c.269C>T	p.Thr90Ile	missense	Exon 4 of 9	ENSP00000414441.2	E9PCW1
	GOSR1	ENST00000225724.9	TSL:1	c.275C>T	p.Thr92Ile	missense	Exon 4 of 9	ENSP00000225724.5	O95249-1
	GOSR1	ENST00000467337.6	TSL:1	c.80C>T	p.Thr27Ile	missense	Exon 4 of 9	ENSP00000462638.1	O95249-2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151320 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.0000679 AC: 16 AN: 235648 AF XY: 0.0000863

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000328

Gnomad ASJ exome AF: 0.000107

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000119

Gnomad OTH exome AF: 0.000178

GnomAD4 exome AF: 0.0000260 AC: 37 AN: 1423656 Hom.: 0 Cov.: 27 AF XY: 0.0000381 AC XY: 27 AN XY: 708920

African (AFR) AF: 0.00 AC: 0 AN: 31642

American (AMR) AF: 0.0000502 AC: 2 AN: 39814

Ashkenazi Jewish (ASJ) AF: 0.000158 AC: 4 AN: 25374

East Asian (EAS) AF: 0.00 AC: 0 AN: 39502

South Asian (SAS) AF: 0.00 AC: 0 AN: 81198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5628

European-Non Finnish (NFE) AF: 0.0000239 AC: 26 AN: 1088398

Other (OTH) AF: 0.0000509 AC: 3 AN: 58952

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151320 Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 2 AN XY: 73796

African (AFR) AF: 0.00 AC: 0 AN: 41094

American (AMR) AF: 0.00 AC: 0 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10366

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67938

Other (OTH) AF: 0.000481 AC: 1 AN: 2078

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000906 AC: 11

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.020	N
PhyloP100		3.6
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.10
Sift	Benign	0.42	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.32
MVP		0.54
MPC		0.17
ClinPred		0.057	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.82
Mutation Taster		=63/37	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: rs369366770; hg19: chr17-28811715;