3-108383733-T-TAA

Variant summary

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

The NM_014981.3(MYH15):c.5632-5_5632-4insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,026,674 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0022 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH15 NM_014981.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.240

Genes affected

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900545 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 3-108383733-T-TAA is Benign according to our data. Variant chr3-108383733-T-TAA is described in ClinVar as [Benign]. Clinvar id is 787974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 280 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH15	NM_014981.3	c.5632-5_5632-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000693548.1
LOC124900545	XR_007095998.1	n.112+2086_112+2087dup		intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3	c.5692-5_5692-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH15	ENST00000693548.1	c.5632-5_5632-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_014981.3	P1
MYH15	ENST00000273353.5	c.5632-5_5632-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P1
MYH15	ENST00000689784.1	c.4651-5_4651-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.00 AC: 240 AN: 58154 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00926

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00632

Gnomad EAS AF: 0.00620

Gnomad SAS AF: 0.00647

Gnomad FIN AF: 0.00391

Gnomad MID AF: 0.0106

Gnomad NFE AF: 0.00518

Gnomad OTH AF: 0.00964

GnomAD3 exomes AF: 0.00498 AC: 280 AN: 56170 Hom.: 1 AF XY: 0.00496 AC XY: 152 AN XY: 30628

Gnomad AFR exome AF: 0.000803

Gnomad AMR exome AF: 0.00618

Gnomad ASJ exome AF: 0.00859

Gnomad EAS exome AF: 0.0104

Gnomad SAS exome AF: 0.00435

Gnomad FIN exome AF: 0.0102

Gnomad NFE exome AF: 0.00473

Gnomad OTH exome AF: 0.00551

GnomAD4 exome AF: 0.00225 AC: 2310 AN: 1026674 Hom.: 2 Cov.: 31 AF XY: 0.00252 AC XY: 1264 AN XY: 502556

Gnomad4 AFR exome AF: 0.00138

Gnomad4 AMR exome AF: 0.00680

Gnomad4 ASJ exome AF: 0.00423

Gnomad4 EAS exome AF: 0.00295

Gnomad4 SAS exome AF: 0.00735

Gnomad4 FIN exome AF: 0.00286

Gnomad4 NFE exome AF: 0.00187

Gnomad4 OTH exome AF: 0.00250

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00412 AC: 240 AN: 58208 Hom.: 0 Cov.: 29 AF XY: 0.00406 AC XY: 112 AN XY: 27568

Gnomad4 AFR AF: 0.00200

Gnomad4 AMR AF: 0.00668

Gnomad4 ASJ AF: 0.00632

Gnomad4 EAS AF: 0.00624

Gnomad4 SAS AF: 0.00653

Gnomad4 FIN AF: 0.00391

Gnomad4 NFE AF: 0.00518

Gnomad4 OTH AF: 0.00959

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs377049870; hg19: chr3-108102580;