rs3758369

chr10-29564583-A-Gchr10-29564583-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021738.3(SVIL):c.-142-1291T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,878 control chromosomes in the GnomAD database, including 14,292 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14292 hom., cov: 31)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SVIL	NM_021738.3	c.-142-1291T>C		intron_variant		ENST00000355867.9
SVIL	NM_001323599.2	c.-142-1291T>C		intron_variant
SVIL	NM_001323600.1	c.-142-1291T>C		intron_variant
SVIL	NM_003174.3	c.-142-1291T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SVIL	ENST00000355867.9	c.-142-1291T>C		intron_variant		1	NM_021738.3	A2

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65635 AN: 151760 Hom.: 14272 Cov.: 31

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.397

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.433 AC: 65700 AN: 151878 Hom.: 14292 Cov.: 31 AF XY: 0.434 AC XY: 32243 AN XY: 74224

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.402

Alfa AF: 0.275 Hom.: 683

Bravo AF: 0.434

Asia WGS AF: 0.473 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.2
Dann	Benign	0.53

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: rs3758369; hg19: chr10-29853512;