17-30522305-G-C

Variant names:

• chr17-30522305-G-C
• rs761237681
• NM_001007025.2:c.674G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001007025.2(GOSR1):​c.674G>C​(p.Arg225Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R225Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GOSR1 NM_001007025.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.30
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.875

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.674G>C	p.Arg225Pro	missense	Exon 9 of 9	NP_001007026.1	E9PCW1
	GOSR1	NM_004871.3		c.680G>C	p.Arg227Pro	missense	Exon 9 of 9	NP_004862.1	O95249-1
	GOSR1	NM_001007024.2		c.485G>C	p.Arg162Pro	missense	Exon 9 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.674G>C	p.Arg225Pro	missense	Exon 9 of 9	ENSP00000414441.2	E9PCW1
	GOSR1	ENST00000225724.9	TSL:1	c.680G>C	p.Arg227Pro	missense	Exon 9 of 9	ENSP00000225724.5	O95249-1
	GOSR1	ENST00000467337.6	TSL:1	c.485G>C	p.Arg162Pro	missense	Exon 9 of 9	ENSP00000462638.1	O95249-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458102 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725380

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 85378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109720

Other (OTH) AF: 0.00 AC: 0 AN: 60242

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		9.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Pathogenic	0.89
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.67		Loss of MoRF binding (P = 0.0074)
MVP		0.74
MPC		0.79
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.90
gMVP		0.98

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: rs761237681; hg19: chr17-28849323;