3-108383733-T-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_014981.3(MYH15):c.5632-4A>T 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 0.00077 in 1,033,904 control chromosomes in the GnomAD database, including 1 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00077 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH15 NM_014981.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00007305
• Clinical Significance: Likely 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 3-108383733-T-A is Benign according to our data. Variant chr3-108383733-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 711388.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 117 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 98 AN: 59174 Hom.: 0 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.000607

Gnomad AMI AF: 0.00301

Gnomad AMR AF: 0.00107

Gnomad ASJ AF: 0.00172

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00320

Gnomad FIN AF: 0.00665

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00222

Gnomad OTH AF: 0.00135

GnomAD3 exomes AF: 0.00208 AC: 117 AN: 56170 Hom.: 0 AF XY: 0.00232 AC XY: 71 AN XY: 30628

Gnomad AFR exome AF: 0.000459

Gnomad AMR exome AF: 0.00251

Gnomad ASJ exome AF: 0.00115

Gnomad EAS exome AF: 0.00410

Gnomad SAS exome AF: 0.00290

Gnomad FIN exome AF: 0.00498

Gnomad NFE exome AF: 0.00194

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000770 AC: 796 AN: 1033904 Hom.: 1 Cov.: 30 AF XY: 0.000912 AC XY: 462 AN XY: 506446

Gnomad4 AFR exome AF: 0.000472

Gnomad4 AMR exome AF: 0.00397

Gnomad4 ASJ exome AF: 0.00216

Gnomad4 EAS exome AF: 0.00111

Gnomad4 SAS exome AF: 0.00378

Gnomad4 FIN exome AF: 0.00214

Gnomad4 NFE exome AF: 0.000497

Gnomad4 OTH exome AF: 0.000759

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00165 AC: 98 AN: 59226 Hom.: 0 Cov.: 17 AF XY: 0.00168 AC XY: 47 AN XY: 27972

Gnomad4 AFR AF: 0.000605

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.00172

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00323

Gnomad4 FIN AF: 0.00665

Gnomad4 NFE AF: 0.00223

Gnomad4 OTH AF: 0.00134

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	12
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000073
dbscSNV1_RF	Benign	0.044
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; COSMIC: COSV56310773;