Variant 10-29458488-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021738.3(SVIL):c.6504G>A(p.Pro2168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,585,330 control chromosomes in the GnomAD database, including 57,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6433 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50753 hom. )

Consequence

SVIL
NM_021738.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.76

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:

SVIL-AS1 (HGNC:51219): (SVIL antisense RNA 1)

SVIL-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 10-29458488-C-T is Benign according to our data. Variant chr10-29458488-C-T is described in ClinVar as [Benign]. Clinvar id is 1268155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVIL	NM_021738.3 linkuse as main transcript	c.6504G>A	p.Pro2168=	synonymous_variant	37/38	ENST00000355867.9	NP_068506.2
SVIL-AS1	NR_110927.1 linkuse as main transcript	n.182-28667C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9 linkuse as main transcript	c.6504G>A	p.Pro2168=	synonymous_variant	37/38	1	NM_021738.3	ENSP00000348128	A2	O95425-1
SVIL-AS1	ENST00000684815.1 linkuse as main transcript	n.236+43076C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42573

AN:

152008

Hom.:

6415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.304

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.257

GnomAD3 exomes

AF:

0.312

AC:

70648

AN:

226782

Hom.:

12568

AF XY:

0.307

AC XY:

37302

AN XY:

121512

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.553

Gnomad SAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.256

AC:

366587

AN:

1433204

Hom.:

50753

Cov.:

AF XY:

0.258

AC XY:

183061

AN XY:

710010

show subpopulations

Gnomad4 AFR exome

AF:

0.292

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.535

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.280

AC:

42639

AN:

152126

Hom.:

6433

Cov.:

AF XY:

0.290

AC XY:

21535

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.304

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.177

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.261

Alfa

AF:

0.245

Hom.:

1480

Bravo

AF:

0.283

Asia WGS

AF:

0.417

AC:

1447

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.65

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over