3-108383733-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_014981.3(MYH15):c.5632-4A>G 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 0.0209 in 1,094,500 control chromosomes in the GnomAD database, including 2,731 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (1474 hom., cov: 17)
  • Exomes 𝑓: 0.011 (1257 hom.)
• Consequence: MYH15 NM_014981.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001012
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.369

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 3-108383733-T-C is Benign according to our data. Variant chr3-108383733-T-C is described in ClinVar as [Benign]. Clinvar id is 767922.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH15	NM_014981.3	c.5632-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000693548.1
LOC124900545	XR_007095998.1	n.112+2082T>C		intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3	c.5692-4A>G		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.5632-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_014981.3	P1
MYH15	ENST00000273353.5	c.5632-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P1
MYH15	ENST00000689784.1	c.4651-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Frequencies

GnomAD3 genomes AF: 0.192 AC: 11400 AN: 59466 Hom.: 1461 Cov.: 17

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0938

Gnomad NFE AF: 0.00405

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.0824 AC: 4630 AN: 56170 Hom.: 607 AF XY: 0.0613 AC XY: 1878 AN XY: 30628

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.0783

Gnomad ASJ exome AF: 0.0550

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00787

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00459

Gnomad OTH exome AF: 0.0561

GnomAD4 exome AF: 0.0111 AC: 11479 AN: 1034982 Hom.: 1257 Cov.: 30 AF XY: 0.00992 AC XY: 5032 AN XY: 507056

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.0379

Gnomad4 ASJ exome AF: 0.0167

Gnomad4 EAS exome AF: 0.0000370

Gnomad4 SAS exome AF: 0.00351

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00126

Gnomad4 OTH exome AF: 0.0270

GnomAD4 genome AF: 0.192 AC: 11448 AN: 59518 Hom.: 1474 Cov.: 17 AF XY: 0.192 AC XY: 5394 AN XY: 28110

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.0896

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00405

Gnomad4 OTH AF: 0.167

Alfa AF: 0.00148 Hom.: 1

Bravo AF: 0.0859

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	13
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.056
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: rs79837783; hg19: chr3-108102580;