10-29458689-T-A

Position:

• chr10-29458689-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021738.3(SVIL):​c.6403-100A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,292,950 control chromosomes in the GnomAD database, including 92,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11048 hom., cov: 33)
  • Exomes 𝑓: 0.37 (81596 hom.)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.37

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 10-29458689-T-A is Benign according to our data. Variant chr10-29458689-T-A is described in ClinVar as [Benign]. Clinvar id is 1248642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	c.6403-100A>T		intron_variant		ENST00000355867.9	NP_068506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.6403-100A>T		intron_variant		1	NM_021738.3	ENSP00000348128.4

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57007 AN: 151960 Hom.: 11030 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.375 AC: 427657 AN: 1140872 Hom.: 81596 Cov.: 15 AF XY: 0.375 AC XY: 212879 AN XY: 568152

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.364

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.375 AC: 57070 AN: 152078 Hom.: 11048 Cov.: 33 AF XY: 0.385 AC XY: 28640 AN XY: 74334

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.348

Alfa AF: 0.377 Hom.: 1353

Bravo AF: 0.371

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.055
DANN	Benign	0.77

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: rs7098527; hg19: chr10-29747618;