chr10-74114909-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014000.3(VCL):​c.3258+10A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 29)

Consequence

VCL
NM_014000.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0930
Variant links:
Genes affected
VCL (HGNC:12665): (vinculin) Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane. Defects in VCL are the cause of cardiomyopathy dilated type 1W. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 10-74114909-A-C is Benign according to our data. Variant chr10-74114909-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1631372.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VCLNM_014000.3 linkuse as main transcriptc.3258+10A>C intron_variant ENST00000211998.10 NP_054706.1
VCLNM_003373.4 linkuse as main transcriptc.3054+10A>C intron_variant NP_003364.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VCLENST00000211998.10 linkuse as main transcriptc.3258+10A>C intron_variant 1 NM_014000.3 ENSP00000211998 P18206-1
VCLENST00000372755.7 linkuse as main transcriptc.3054+10A>C intron_variant 1 ENSP00000361841 P1P18206-2
VCLENST00000623461.3 linkuse as main transcriptn.5857+10A>C intron_variant, non_coding_transcript_variant 1
VCLENST00000624354.3 linkuse as main transcriptc.*3013+10A>C intron_variant, NMD_transcript_variant 2 ENSP00000485551

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
29

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1W Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 15, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
1.4
DANN
Benign
0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-75874667; API