Variant 10-29532594-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021738.3(SVIL):c.1773A>C(p.Lys591Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SVIL
NM_021738.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]

SVIL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.24878436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3 linkuse as main transcript	c.1773A>C	p.Lys591Asn	missense_variant	8/38	ENST00000355867.9	NP_068506.2	O95425-1Q569J5
SVIL	NM_001323599.2 linkuse as main transcript	c.909-422A>C		intron_variant			NP_001310528.1	A0A6I8PIX7
SVIL	NM_001323600.1 linkuse as main transcript	c.828-1306A>C		intron_variant			NP_001310529.1
SVIL	NM_003174.3 linkuse as main transcript	c.828-1306A>C		intron_variant			NP_003165.2	O95425-2Q569J5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SVIL	ENST00000355867.9 linkuse as main transcript	c.1773A>C	p.Lys591Asn	missense_variant	8/38	1	NM_021738.3	ENSP00000348128.4	O95425-1
SVIL	ENST00000375400.7 linkuse as main transcript	c.828-1306A>C		intron_variant		1		ENSP00000364549.3	O95425-2
SVIL	ENST00000375398.6 linkuse as main transcript	c.1773A>C	p.Lys591Asn	missense_variant	8/37	5		ENSP00000364547.3	O95425-4
SVIL	ENST00000674475.1 linkuse as main transcript	c.909-422A>C		intron_variant				ENSP00000501521.1	A0A6I8PIX7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251182

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135754

show subpopulations

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727120

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

.;T

Eigen

Benign

0.068

Eigen_PC

Benign

0.085

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.051

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.93

.;P

Vest4

0.42

MutPred

0.36

Loss of ubiquitination at K591 (P = 0.0071);Loss of ubiquitination at K591 (P = 0.0071);

MVP

0.43

MPC

0.59

ClinPred

0.86

GERP RS

4.5

Varity_R

0.18

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over