Variant 3-108389081-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_014981.3(MYH15):c.5431-7G>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 0.000844 in 1,613,446 control chromosomes in the GnomAD database, including 11 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 0.0047 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 5 hom. )

Consequence

MYH15
NM_014981.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004379

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.498

Variant links:

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]

MYH15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 3-108389081-C-A is Benign according to our data. Variant chr3-108389081-C-A is described in ClinVar as [Benign]. Clinvar id is 723897.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00466 (709/152252) while in subpopulation AFR AF= 0.0161 (670/41538). AF 95% confidence interval is 0.0151. There are 6 homozygotes in gnomad4. There are 322 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 709 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH15	NM_014981.3 linkuse as main transcript	c.5431-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000693548.1	NP_055796.2
MYH15	XM_011512559.3 linkuse as main transcript	c.5491-7G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
MYH15	ENST00000693548.1 linkuse as main transcript	c.5431-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.5431-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000273353	P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.4450-7G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			ENSP00000509841

Frequencies

GnomAD3 genomes

AF:

0.00466

AC:

709

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00121

AC:

300

AN:

248558

Hom.:

AF XY:

0.000964

AC XY:

130

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.000960

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000446

AC:

652

AN:

1461194

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

283

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00466

AC:

709

AN:

152252

Hom.:

Cov.:

AF XY:

0.00433

AC XY:

322

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00244

Hom.:

Bravo

AF:

0.00542

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.4

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.034

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over