rs10817033

Positions:

• chr9-110496872-T-A
• chr9-110496872-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153366.4(SVEP1):​c.1743A>T​(p.Gln581His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SVEP1 NM_153366.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17433715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.1743A>T	p.Gln581His	missense_variant	8/48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.1743A>T	p.Gln581His	missense_variant	8/48	5	NM_153366.4	ENSP00000363593	P1
SVEP1	ENST00000374461.1	c.1743A>T	p.Gln581His	missense_variant	8/14	1		ENSP00000363585
SVEP1	ENST00000467821.1	n.1162A>T		non_coding_transcript_exon_variant	7/26	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406084 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 694022

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: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	.;M;M
MutationTaster	Benign	0.96	P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.0	D;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D;.;.
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0, 0.028	.;D;B
Vest4		0.055
MutPred		0.23		Loss of catalytic residue at Q581 (P = 0.0581);Loss of catalytic residue at Q581 (P = 0.0581);Loss of catalytic residue at Q581 (P = 0.0581);
MVP		0.23
MPC		0.096
ClinPred		0.97	D
GERP RS		0.97
Varity_R		0.49
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

Publications

LitVar

Other links and lift over

dbSNP: rs10817033; hg19: chr9-113259152;