NM_153366.4:c.10225G>T

Variant names:

• chr9-110385910-C-A
• rs767551252
• NM_153366.4:c.10225G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153366.4(SVEP1):​c.10225G>T​(p.Ala3409Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 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)
• Consequence: SVEP1 NM_153366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3103316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.10225G>T	p.Ala3409Ser	missense_variant	Exon 43 of 48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.10225G>T	p.Ala3409Ser	missense_variant	Exon 43 of 48	5	NM_153366.4	ENSP00000363593.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247306 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.41	T
REVEL	Benign	0.16
Sift4G	Benign	0.11	T;T
Polyphen		0.91	.;P
Vest4		0.19
MutPred		0.73		.;Gain of disorder (P = 0.0149);
MVP		0.043
MPC		0.38
ClinPred		0.92	D
GERP RS		5.1
Varity_R		0.15
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767551252; hg19: chr9-113148190;