9-110387357-T-G

Variant names:

• chr9-110387357-T-G
• rs372409135
• NM_153366.4:c.9988A>C

Variant summary

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

The NM_153366.4(SVEP1):​c.9988A>C​(p.Ser3330Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,474 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SVEP1 NM_153366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74

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.9988A>C	p.Ser3330Arg	missense_variant	Exon 42 of 48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.9988A>C	p.Ser3330Arg	missense_variant	Exon 42 of 48	5	NM_153366.4	ENSP00000363593.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461474 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Benign	0.0073	T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.52	.;N
PrimateAI	Benign	0.38	T
REVEL	Benign	0.14
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.88	.;P
Vest4		0.65
MutPred		0.57		.;Gain of catalytic residue at S3330 (P = 0.0118);
MVP		0.043
MPC		0.32
ClinPred		0.87	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs372409135; hg19: chr9-113149637;