Variant 3-108428881-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014981.3(MYH15):c.3313A>G(p.Thr1105Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,593,946 control chromosomes in the GnomAD database, including 63,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4824 hom., cov: 31)

Exomes 𝑓: 0.28 ( 58483 hom. )

Consequence

MYH15
NM_014981.3 missense, splice_region

Scores

Splicing: ADA: 0.00004654

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002068162).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH15	NM_014981.3 linkuse as main transcript	c.3313A>G	p.Thr1105Ala	missense_variant, splice_region_variant	27/41	ENST00000693548.1	NP_055796.2
MYH15	XM_011512559.3 linkuse as main transcript	c.3373A>G	p.Thr1125Ala	missense_variant, splice_region_variant	29/43		XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH15	ENST00000693548.1 linkuse as main transcript	c.3313A>G	p.Thr1105Ala	missense_variant, splice_region_variant	27/41		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.3313A>G	p.Thr1105Ala	missense_variant, splice_region_variant	28/42	1		ENSP00000273353	P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.2332A>G	p.Thr778Ala	missense_variant, splice_region_variant	19/33			ENSP00000509841
MYH15	ENST00000478998.5 linkuse as main transcript	n.1365A>G		splice_region_variant, non_coding_transcript_exon_variant	10/16	2

Frequencies

GnomAD3 genomes

AF:

0.236

AC:

35857

AN:

151836

Hom.:

4822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.00810

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.306

Gnomad OTH

AF:

0.240

GnomAD3 exomes

AF:

0.240

AC:

55910

AN:

233408

Hom.:

7658

AF XY:

0.244

AC XY:

30948

AN XY:

126716

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.00696

Gnomad SAS exome

AF:

0.208

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.278

AC:

400714

AN:

1441992

Hom.:

58483

Cov.:

AF XY:

0.276

AC XY:

198069

AN XY:

716526

show subpopulations

Gnomad4 AFR exome

AF:

0.151

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.00392

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.236

AC:

35869

AN:

151954

Hom.:

4824

Cov.:

AF XY:

0.232

AC XY:

17252

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.243

Gnomad4 EAS

AF:

0.00792

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.306

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.284

Hom.:

15356

Bravo

AF:

0.224

TwinsUK

AF:

0.299

AC:

1107

ALSPAC

AF:

0.296

AC:

1142

ESP6500AA

AF:

0.142

AC:

524

ESP6500EA

AF:

0.288

AC:

2352

ExAC

AF:

0.238

AC:

28769

Asia WGS

AF:

0.136

AC:

474

AN:

3478

EpiCase

AF:

0.308

EpiControl

AF:

0.307

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.7

DANN

Benign

0.12

DEOGEN2

Benign

0.040

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.65

M_CAP

Benign

0.014

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.82

MutationTaster

Benign

0.34

PrimateAI

Benign

0.31

PROVEAN

Benign

1.4

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.027

MPC

0.079

ClinPred

0.0032

GERP RS

-1.7

Varity_R

0.024

gMVP

0.043

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over