rs3758369

Variant names:

• chr10-29564583-A-G
• rs3758369
• NM_021738.3:c.-142-1291T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-29564583-A-G
• chr10-29564583-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• myofibrillar myopathy 10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SVIL	NM_021738.3	c.-142-1291T>C		intron_variant	Intron 2 of 37	ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.-142-1291T>C		intron_variant	Intron 4 of 38		NP_001310528.1
SVIL	NM_001323600.1	c.-142-1291T>C		intron_variant	Intron 4 of 36		NP_001310529.1
SVIL	NM_003174.3	c.-142-1291T>C		intron_variant	Intron 4 of 35		NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.-142-1291T>C		intron_variant	Intron 2 of 37	1	NM_021738.3	ENSP00000348128.4

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

African (AFR) AF: 0.467 AC: 19339 AN: 41404

American (AMR) AF: 0.441 AC: 6731 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3464

East Asian (EAS) AF: 0.435 AC: 2231 AN: 5124

South Asian (SAS) AF: 0.427 AC: 2052 AN: 4802

European-Finnish (FIN) AF: 0.466 AC: 4918 AN: 10554

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28050 AN: 67948

Other (OTH) AF: 0.402 AC: 847 AN: 2108

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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3758369; hg19: chr10-29853512;