chr14-23389062-A-T

Position:

• chr14-23389062-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002471.4(MYH6):​c.3979-7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000078 (0 hom., cov: 26)
  • Exomes 𝑓: 0.00097 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH6 NM_002471.4 splice_region, intron
• Scores: Splicing: ADA: 0.01137
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

Genes affected

MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH6	NM_002471.4	c.3979-7T>A		splice_region_variant, intron_variant		ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9	c.3979-7T>A		splice_region_variant, intron_variant		5	NM_002471.4	ENSP00000386041.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 9 AN: 115618 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.0000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000355

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000657

Gnomad SAS AF: 0.000291

Gnomad FIN AF: 0.000141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000968 AC: 1025 AN: 1058436 Hom.: 0 Cov.: 27 AF XY: 0.000857 AC XY: 452 AN XY: 527482

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000203

Gnomad4 ASJ exome AF: 0.000775

Gnomad4 EAS exome AF: 0.00126

Gnomad4 SAS exome AF: 0.000153

Gnomad4 FIN exome AF: 0.000171

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.000909

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000778 AC: 9 AN: 115732 Hom.: 0 Cov.: 26 AF XY: 0.0000352 AC XY: 2 AN XY: 56878

Gnomad4 AFR AF: 0.0000257

Gnomad4 AMR AF: 0.000354

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000659

Gnomad4 SAS AF: 0.000291

Gnomad4 FIN AF: 0.000141

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.9
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.011
dbscSNV1_RF	Benign	0.16
SpliceAI score (max)		0.070		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: chr14-23858271;