Variant 3-108383654-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_014981.3(MYH15):c.5707G>C(p.Glu1903Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,612,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

MYH15
NM_014981.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

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:

LOC124900545 (HGNC:):

LOC124900545 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.41213614).

BS2

High AC in GnomAdExome4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH15	NM_014981.3 linkuse as main transcript	c.5707G>C	p.Glu1903Gln	missense_variant	40/41	ENST00000693548.1	NP_055796.2
LOC124900545	XR_007095998.1 linkuse as main transcript	n.112+2003C>G		intron_variant, non_coding_transcript_variant
MYH15	XM_011512559.3 linkuse as main transcript	c.5767G>C	p.Glu1923Gln	missense_variant	42/43		XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH15	ENST00000693548.1 linkuse as main transcript	c.5707G>C	p.Glu1903Gln	missense_variant	40/41		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.5707G>C	p.Glu1903Gln	missense_variant	41/42	1		ENSP00000273353	P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.4726G>C	p.Glu1576Gln	missense_variant	32/33			ENSP00000509841

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249198

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1461162

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

726906

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151546

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73930

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2023

The c.5767G>C (p.E1923Q) alteration is located in exon 41 (coding exon 41) of the MYH15 gene. This alteration results from a G to C substitution at nucleotide position 5767, causing the glutamic acid (E) at amino acid position 1923 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.044

MetaRNN

Benign

0.41

MetaSVM

Uncertain

0.26

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

0.90

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.99

Vest4

0.17

MutPred

0.50

Gain of MoRF binding (P = 0.0246);

MVP

0.85

MPC

0.45

ClinPred

0.91

GERP RS

1.9

Varity_R

0.21

gMVP

0.14

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