rs1328327

Variant names:

• chr10-29575441-C-T
• rs1328327
• NM_021738.3:c.-200-6129G>A

Variant summary

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

The NM_021738.3(SVIL):​c.-200-6129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 204,134 control chromosomes in the GnomAD database, including 29,911 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 0.55 (23330 hom., cov: 33)
  • Exomes 𝑓: 0.50 (6581 hom.)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

SNORD115 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 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.-200-6129G>A		intron	N/A	NP_068506.2	O95425-1
	SVIL	NM_001323599.2		c.-200-6129G>A		intron	N/A	NP_001310528.1	A0A6I8PIX7
	SVIL	NM_001323600.1		c.-200-6129G>A		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.-200-6129G>A		intron	N/A	ENSP00000348128.4	O95425-1
	SVIL	ENST00000375400.7	TSL:1	c.-200-6129G>A		intron	N/A	ENSP00000364549.3	O95425-2
	SVIL	ENST00000860295.1		c.-200-6129G>A		intron	N/A	ENSP00000530354.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82955 AN: 151968 Hom.: 23277 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.500 AC: 26033 AN: 52048 Hom.: 6581 AF XY: 0.489 AC XY: 14956 AN XY: 30564

African (AFR) AF: 0.707 AC: 1233 AN: 1744

American (AMR) AF: 0.630 AC: 4437 AN: 7040

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 242 AN: 730

East Asian (EAS) AF: 0.489 AC: 1841 AN: 3762

South Asian (SAS) AF: 0.508 AC: 2729 AN: 5368

European-Finnish (FIN) AF: 0.489 AC: 1893 AN: 3870

Middle Eastern (MID) AF: 0.359 AC: 197 AN: 548

European-Non Finnish (NFE) AF: 0.463 AC: 12454 AN: 26894

Other (OTH) AF: 0.481 AC: 1007 AN: 2092

GnomAD4 genome AF: 0.546 AC: 83068 AN: 152086 Hom.: 23330 Cov.: 33 AF XY: 0.547 AC XY: 40671 AN XY: 74344

African (AFR) AF: 0.689 AC: 28605 AN: 41490

American (AMR) AF: 0.583 AC: 8908 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1160 AN: 3466

East Asian (EAS) AF: 0.487 AC: 2518 AN: 5172

South Asian (SAS) AF: 0.513 AC: 2471 AN: 4816

European-Finnish (FIN) AF: 0.496 AC: 5242 AN: 10570

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

European-Non Finnish (NFE) AF: 0.477 AC: 32407 AN: 67966

Other (OTH) AF: 0.519 AC: 1098 AN: 2114

Alfa AF: 0.499 Hom.: 25706

Bravo AF: 0.559

Asia WGS AF: 0.540 AC: 1876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.60
PhyloP100		-0.31
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: rs1328327; hg19: chr10-29864370; COSMIC: COSV63439240; COSMIC: COSV63439240;