9-110377326-T-G

Position:

• chr9-110377326-T-G

Variant summary

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

The NM_153366.4(SVEP1):​c.10449A>C​(p.Gln3483His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SVEP1 NM_153366.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0760

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=0.2776242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVEP1	NM_153366.4	c.10449A>C	p.Gln3483His	missense_variant	45/48	ENST00000374469.6	NP_699197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVEP1	ENST00000374469.6	c.10449A>C	p.Gln3483His	missense_variant	45/48	5	NM_153366.4	ENSP00000363593	P1
SVEP1	ENST00000476205.1	n.73A>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.10449A>C (p.Q3483H) alteration is located in exon 45 (coding exon 45) of the SVEP1 gene. This alteration results from a A to C substitution at nucleotide position 10449, causing the glutamine (Q) at amino acid position 3483 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.19	.;N
MutationTaster	Benign	0.93	D;N;N
PrimateAI	Uncertain	0.50	T
REVEL	Benign	0.17
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.97	.;D
Vest4		0.45
MutPred		0.49		.;Gain of catalytic residue at Q3483 (P = 0.0579);
MVP		0.043
MPC		0.39
ClinPred		0.89	D
GERP RS		-2.7
Varity_R		0.19
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-113139606;