rs774876976

Variant names:

• chr9-110375430-C-G
• rs774876976
• NM_153366.4:c.10538G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-110375430-C-G
• chr9-110375430-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153366.4(SVEP1):​c.10538G>C​(p.Arg3513Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: SVEP1 NM_153366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

Genes affected

SVEP1 (HGNC:15985): (sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1) Predicted to enable calcium ion binding activity and chromatin binding activity. Predicted to be involved in epidermis development and lymph vessel morphogenesis. Predicted to act upstream of or within several processes, including Tie signaling pathway; lymph circulation; and lymph vessel development. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.10538G>C	p.Arg3513Pro	missense_variant	Exon 46 of 48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.10538G>C	p.Arg3513Pro	missense_variant	Exon 46 of 48	5	NM_153366.4	ENSP00000363593.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Uncertain	0.54	T
REVEL	Uncertain	0.35
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	.;D
Vest4		0.86
MutPred		0.61		.;Gain of disorder (P = 0.0819);
MVP		0.093
MPC		0.56
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.72
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs774876976; hg19: chr9-113137710;