10-29622639-G-A

Variant names:

• chr10-29622639-G-A
• rs1777329
• NM_021738.3:c.-201+11781C>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.-201+11781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,160 control chromosomes in the GnomAD database, including 782 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 0.091 (782 hom., cov: 32)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 1 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 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.-201+11781C>T		intron	N/A	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.-201+35330C>T		intron	N/A	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.-201+35330C>T		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.-201+11781C>T		intron	N/A	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.-201+35330C>T		intron	N/A	ENSP00000364549.3	O95425-2
	SVIL	ENST00000860295.1		c.-201+11781C>T		intron	N/A	ENSP00000530354.1

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13848 AN: 152042 Hom.: 783 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0911 AC: 13857 AN: 152160 Hom.: 782 Cov.: 32 AF XY: 0.0889 AC XY: 6614 AN XY: 74384

African (AFR) AF: 0.0612 AC: 2542 AN: 41512

American (AMR) AF: 0.136 AC: 2075 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 637 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0879 AC: 424 AN: 4822

European-Finnish (FIN) AF: 0.0789 AC: 834 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6921 AN: 68002

Other (OTH) AF: 0.115 AC: 242 AN: 2108

Alfa AF: 0.0910 Hom.: 381

Bravo AF: 0.0940

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.63
DANN	Benign	0.67
PhyloP100		-1.2
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: rs1777329; hg19: chr10-29911568;