Variant 3-108394107-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014981.3(MYH15):c.5183G>A(p.Arg1728Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00721 in 1,614,074 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 81 hom. )

Consequence

MYH15
NM_014981.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0160

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004033953).

BP6

Variant 3-108394107-C-T is Benign according to our data. Variant chr3-108394107-C-T is described in ClinVar as [Benign]. Clinvar id is 774603.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 944 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH15	NM_014981.3 linkuse as main transcript	c.5183G>A	p.Arg1728Gln	missense_variant	36/41	ENST00000693548.1
MYH15	XM_011512559.3 linkuse as main transcript	c.5243G>A	p.Arg1748Gln	missense_variant	38/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYH15	ENST00000693548.1 linkuse as main transcript	c.5183G>A	p.Arg1728Gln	missense_variant	36/41		NM_014981.3	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.5183G>A	p.Arg1728Gln	missense_variant	37/42	1		P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.4202G>A	p.Arg1401Gln	missense_variant	28/33

Frequencies

GnomAD3 genomes

AF:

0.00620

AC:

944

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.0199

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00866

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00790

AC:

1969

AN:

249144

Hom.:

AF XY:

0.00834

AC XY:

1127

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.00961

Gnomad OTH exome

AF:

0.00727

GnomAD4 exome

AF:

0.00732

AC:

10701

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00746

AC XY:

5425

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.00740

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.00619

AC:

942

AN:

152284

Hom.:

Cov.:

AF XY:

0.00663

AC XY:

494

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00808

Gnomad4 FIN

AF:

0.0199

Gnomad4 NFE

AF:

0.00864

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00687

Hom.:

Bravo

AF:

0.00446

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000751

AC:

ESP6500EA

AF:

0.00753

AC:

ExAC

AF:

0.00847

AC:

1024

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00654

EpiControl

AF:

0.00551

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

Cadd

Benign

0.15

Dann

Benign

0.39

DEOGEN2

Benign

0.040

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.73

MutationTaster

Benign

1.0

PrimateAI

Benign

0.18

PROVEAN

Benign

2.2

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0050

Vest4

0.11

MVP

0.26

MPC

0.093

ClinPred

0.00030

GERP RS

-3.5

Varity_R

0.019

gMVP

0.045

Splicing

Name

Calibrated prediction

Score

Prediction

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