chr10-29570950-G-A

Variant names:

• chr10-29570950-G-A
• rs1328326
• NM_021738.3:c.-200-1638C>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.-200-1638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,012 control chromosomes in the GnomAD database, including 22,863 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 0.54 (22863 hom., cov: 33)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021738.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	NM_021738.3	MANE Select	c.-200-1638C>T		intron	N/A	NP_068506.2
	SVIL	NM_001323599.2		c.-200-1638C>T		intron	N/A	NP_001310528.1
	SVIL	NM_001323600.1		c.-200-1638C>T		intron	N/A	NP_001310529.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.-200-1638C>T		intron	N/A	ENSP00000348128.4
	SVIL	ENST00000375400.7	TSL:1	c.-200-1638C>T		intron	N/A	ENSP00000364549.3
	SVIL	ENST00000375398.6	TSL:5	c.-200-1638C>T		intron	N/A	ENSP00000364547.3

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82377 AN: 151894 Hom.: 22812 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.543 AC: 82486 AN: 152012 Hom.: 22863 Cov.: 33 AF XY: 0.545 AC XY: 40462 AN XY: 74290

African (AFR) AF: 0.665 AC: 27572 AN: 41460

American (AMR) AF: 0.583 AC: 8905 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.486 AC: 2506 AN: 5160

South Asian (SAS) AF: 0.513 AC: 2472 AN: 4818

European-Finnish (FIN) AF: 0.524 AC: 5523 AN: 10548

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32567 AN: 67974

Other (OTH) AF: 0.516 AC: 1087 AN: 2108

Alfa AF: 0.486 Hom.: 29868

Bravo AF: 0.553

Asia WGS AF: 0.536 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.39
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1328326; hg19: chr10-29859879; COSMIC: COSV63442906; COSMIC: COSV63442906;