rs193922652

chr14-23389062-AGGG-Achr14-23389062-AGGG-AGchr14-23389062-AGGG-AGGchr14-23389062-AGGG-AGGGGchr14-23389062-AGGG-AGGGGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002471.4(MYH6):c.3979-10_3979-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000043 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000060 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH6 NM_002471.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

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 -6 ACMG points.

• BP6: Variant 14-23389062-AGGG-A is Benign according to our data. Variant chr14-23389062-AGGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 239169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4	c.3979-10_3979-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9	c.3979-10_3979-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_002471.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000432 AC: 5 AN: 115624 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000853

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000604 AC: 64 AN: 1059204 Hom.: 1 AF XY: 0.0000606 AC XY: 32 AN XY: 527874

Gnomad4 AFR exome AF: 0.0000329

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000153

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000760

Gnomad4 OTH exome AF: 0.0000221

GnomAD4 genome AF: 0.0000432 AC: 5 AN: 115624 Hom.: 0 Cov.: 0 AF XY: 0.0000705 AC XY: 4 AN XY: 56768

Gnomad4 AFR AF: 0.0000258

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000853

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypertrophic cardiomyopathy 14 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 25, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs193922652; hg19: chr14-23858271;