3-108383737-A-AAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014981.3(MYH15):c.5632-9_5632-8insGT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,382,330 control chromosomes in the GnomAD database, including 7,135 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (4056 hom., cov: 0)
  • Exomes 𝑓: 0.15 (3079 hom.)
• Consequence: MYH15 NM_014981.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.33

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 3-108383737-A-AAC is Benign according to our data. Variant chr3-108383737-A-AAC is described in ClinVar as [Benign]. Clinvar id is 769277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH15	NM_014981.3	c.5632-9_5632-8insGT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000693548.1
LOC124900545	XR_007095998.1	n.112+2087_112+2088insCA		intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3	c.5692-9_5692-8insGT		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH15	ENST00000693548.1	c.5632-9_5632-8insGT		splice_polypyrimidine_tract_variant, intron_variant			NM_014981.3	P1
MYH15	ENST00000273353.5	c.5632-9_5632-8insGT		splice_polypyrimidine_tract_variant, intron_variant		1		P1
MYH15	ENST00000689784.1	c.4651-9_4651-8insGT		splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.312 AC: 35011 AN: 112128 Hom.: 4060 Cov.: 0

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.337

GnomAD3 exomes AF: 0.0661 AC: 8876 AN: 134344 Hom.: 500 AF XY: 0.0604 AC XY: 4573 AN XY: 75756

Gnomad AFR exome AF: 0.0900

Gnomad AMR exome AF: 0.0949

Gnomad ASJ exome AF: 0.0655

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.0367

Gnomad FIN exome AF: 0.0161

Gnomad NFE exome AF: 0.0677

Gnomad OTH exome AF: 0.0883

GnomAD4 exome AF: 0.153 AC: 193750 AN: 1270198 Hom.: 3079 Cov.: 29 AF XY: 0.149 AC XY: 94051 AN XY: 631674

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0918

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.0857

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.312 AC: 34994 AN: 112132 Hom.: 4056 Cov.: 0 AF XY: 0.309 AC XY: 16766 AN XY: 54202

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.335

Alfa AF: 0.205 Hom.: 120

Asia WGS AF: 0.148 AC: 499 AN: 3364

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

Dec 31, 2019

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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: rs141454667; hg19: chr3-108102584;