10-29558518-C-G

Variant names:

• chr10-29558518-C-G
• rs7903397
• NM_021738.3:c.-50-3410G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021738.3(SVIL):​c.-50-3410G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,842 control chromosomes in the GnomAD database, including 7,092 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 0.30 (7092 hom., cov: 32)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• Publications: 3 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, MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics

SVIL-AS1 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	NM_021738.3	MANE Select	c.-50-3410G>C		intron	N/A	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.-50-3410G>C		intron	N/A	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.-50-3410G>C		intron	N/A	NP_001310529.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVIL	ENST00000355867.9	TSL:1 MANE Select	c.-50-3410G>C		intron	N/A	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.-50-3410G>C		intron	N/A	ENSP00000364549.3	O95425-2
	SVIL	ENST00000860295.1		c.-50-3410G>C		intron	N/A	ENSP00000530354.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45467 AN: 151722 Hom.: 7084 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.300 AC: 45497 AN: 151842 Hom.: 7092 Cov.: 32 AF XY: 0.300 AC XY: 22236 AN XY: 74218

African (AFR) AF: 0.385 AC: 15932 AN: 41384

American (AMR) AF: 0.287 AC: 4372 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3466

East Asian (EAS) AF: 0.330 AC: 1700 AN: 5158

South Asian (SAS) AF: 0.247 AC: 1188 AN: 4800

European-Finnish (FIN) AF: 0.293 AC: 3084 AN: 10512

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17611 AN: 67966

Other (OTH) AF: 0.269 AC: 567 AN: 2106

Alfa AF: 0.283 Hom.: 812

Bravo AF: 0.304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		0.34
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: rs7903397; hg19: chr10-29847447;