17-46931204-G-C

Variant names:

• chr17-46931204-G-C
• rs197922
• NM_004287.5:c.200G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004287.5(GOSR2):​c.200G>C​(p.Arg67Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. R67Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOSR2 NM_004287.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76
• Publications: 80 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28334457).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004287.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	NM_004287.5	MANE Select	c.200G>C	p.Arg67Thr	missense	Exon 3 of 6	NP_004278.2
	GOSR2	NM_001321133.2		c.200G>C	p.Arg67Thr	missense	Exon 3 of 7	NP_001308062.1
	GOSR2	NM_054022.4		c.200G>C	p.Arg67Thr	missense	Exon 3 of 7	NP_473363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.200G>C	p.Arg67Thr	missense	Exon 3 of 6	ENSP00000492751.1
	GOSR2	ENST00000225567.9	TSL:1	c.200G>C	p.Arg67Thr	missense	Exon 3 of 7	ENSP00000225567.4
	GOSR2	ENST00000640621.1	TSL:1	c.200G>C	p.Arg67Thr	missense	Exon 3 of 5	ENSP00000492830.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.031
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.14	B
Vest4		0.21
MutPred		0.49		Loss of MoRF binding (P = 0.0204)
MVP		0.50
MPC		0.37
ClinPred		0.96	D
GERP RS		4.8
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.33

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: rs197922; hg19: chr17-45008570;