NM_021738.3:c.4193-585A>C

Variant names:

• chr10-29489341-T-G
• rs12358834
• NM_021738.3:c.4193-585A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021738.3(SVIL):​c.4193-585A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,252 control chromosomes in the GnomAD database, including 867 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 0.095 (867 hom., cov: 32)
• Consequence: SVIL NM_021738.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIL	NM_021738.3	c.4193-585A>C		intron_variant	Intron 22 of 37	ENST00000355867.9	NP_068506.2
SVIL	NM_001323599.2	c.3263-585A>C		intron_variant	Intron 23 of 38		NP_001310528.1
SVIL	NM_001323600.1	c.3011-585A>C		intron_variant	Intron 21 of 36		NP_001310529.1
SVIL	NM_003174.3	c.2915-585A>C		intron_variant	Intron 20 of 35		NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000355867.9	c.4193-585A>C		intron_variant	Intron 22 of 37	1	NM_021738.3	ENSP00000348128.4

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14459 AN: 152134 Hom.: 868 Cov.: 32

Gnomad AFR AF: 0.0471

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.0870

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

GnomAD4 genome AF: 0.0949 AC: 14456 AN: 152252 Hom.: 867 Cov.: 32 AF XY: 0.0957 AC XY: 7123 AN XY: 74444

Gnomad4 AFR AF: 0.0470

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.0861

Alfa AF: 0.118 Hom.: 1085

Bravo AF: 0.0882

Asia WGS AF: 0.0190 AC: 69 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs12358834; hg19: chr10-29778270;