3-108383733-T-TA

Position:

• chr3-108383733-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014981.3(MYH15):​c.5632-5_5632-4insT 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 0.00271 in 1,028,758 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0027 (0 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 3-108383733-T-TA is Benign according to our data. Variant chr3-108383733-T-TA is described in ClinVar as [Benign]. Clinvar id is 791941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00271 (2786/1028758) while in subpopulation AMR AF= 0.0266 (410/15414). AF 95% confidence interval is 0.0245. There are 0 homozygotes in gnomad4_exome. There are 1678 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 2786 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH15	NM_014981.3	c.5632-5_5632-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000693548.1	NP_055796.2
LOC124900545	XR_007095998.1	n.112+2087dup		intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3	c.5692-5_5692-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH15	ENST00000693548.1	c.5632-5_5632-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5	c.5632-5_5632-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000273353	P1
MYH15	ENST00000689784.1	c.4651-5_4651-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000509841

Frequencies

GnomAD3 genomes AF: 0.00 AC: 126 AN: 58940 Hom.: 0 Cov.: 29 FAILED QC

Gnomad AFR AF: 0.00243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

Gnomad ASJ AF: 0.00175

Gnomad EAS AF: 0.00711

Gnomad SAS AF: 0.000805

Gnomad FIN AF: 0.00195

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00542

GnomAD3 exomes AF: 0.0233 AC: 1309 AN: 56170 Hom.: 0 AF XY: 0.0227 AC XY: 695 AN XY: 30628

Gnomad AFR exome AF: 0.00688

Gnomad AMR exome AF: 0.0241

Gnomad ASJ exome AF: 0.0241

Gnomad EAS exome AF: 0.0377

Gnomad SAS exome AF: 0.0300

Gnomad FIN exome AF: 0.0498

Gnomad NFE exome AF: 0.0222

Gnomad OTH exome AF: 0.0257

GnomAD4 exome AF: 0.00271 AC: 2786 AN: 1028758 Hom.: 0 Cov.: 31 AF XY: 0.00333 AC XY: 1678 AN XY: 503402

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.0266

Gnomad4 ASJ exome AF: 0.00504

Gnomad4 EAS exome AF: 0.00435

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.00885

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00214 AC: 126 AN: 58992 Hom.: 0 Cov.: 29 AF XY: 0.00226 AC XY: 63 AN XY: 27902

Gnomad4 AFR AF: 0.00242

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.00175

Gnomad4 EAS AF: 0.00714

Gnomad4 SAS AF: 0.000812

Gnomad4 FIN AF: 0.00195

Gnomad4 NFE AF: 0.00191

Gnomad4 OTH AF: 0.00539

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs377049870; hg19: chr3-108102580;