NM_004287.5:c.200G>T

Variant names:

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

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>T​(p.Arg67Ile) 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. 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=0.37050533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOSR2	NM_004287.5	c.200G>T	p.Arg67Ile	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.200G>T	p.Arg67Ile	missense_variant	Exon 3 of 6	1	NM_004287.5	ENSP00000492751.1
ENSG00000262633	ENST00000571841.1	n.200G>T		non_coding_transcript_exon_variant	Exon 3 of 10	5		ENSP00000461460.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 43667

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	0.049
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D;.;D;D;.;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.37	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	-0.56	T
MutationAssessor	Benign	1.1	.;.;.;L;.;.;L;.;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.
PhyloP100		3.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.2	.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0010	.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.0030	.;.;.;D;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.
Polyphen		0.54, 0.41	.;.;.;P;.;.;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.32, 0.41
MutPred		0.53		Loss of methylation at R67 (P = 0.0222);.;Loss of methylation at R67 (P = 0.0222);Loss of methylation at R67 (P = 0.0222);.;.;Loss of methylation at R67 (P = 0.0222);Loss of methylation at R67 (P = 0.0222);Loss of methylation at R67 (P = 0.0222);.;.;Loss of methylation at R67 (P = 0.0222);.;.;.;Loss of methylation at R67 (P = 0.0222);.;.;.;.;.;.;.;
MVP		0.62
MPC		0.67
ClinPred		0.99	D
GERP RS		4.8
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.38

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;