Variant 3-108381559-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_014981.3(MYH15):c.5767G>T(p.Val1923Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,613,798 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

MYH15
NM_014981.3 missense, splice_region

Scores

Splicing: ADA: 0.8490

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.462

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 -6 ACMG points.

BP6

Variant 3-108381559-C-A is Benign according to our data. Variant chr3-108381559-C-A is described in ClinVar as [Benign]. Clinvar id is 709753.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 263 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH15	NM_014981.3 linkuse as main transcript	c.5767G>T	p.Val1923Phe	missense_variant, splice_region_variant	41/41	ENST00000693548.1	NP_055796.2
LOC124900545	XR_007095998.1 linkuse as main transcript	n.20C>A		non_coding_transcript_exon_variant	1/2
MYH15	XM_011512559.3 linkuse as main transcript	c.5827G>T	p.Val1943Phe	missense_variant, splice_region_variant	43/43		XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH15	ENST00000693548.1 linkuse as main transcript	c.5767G>T	p.Val1923Phe	missense_variant, splice_region_variant	41/41		NM_014981.3	ENSP00000508967	P1
MYH15	ENST00000273353.5 linkuse as main transcript	c.5767G>T	p.Val1923Phe	missense_variant, splice_region_variant	42/42	1		ENSP00000273353	P1
MYH15	ENST00000689784.1 linkuse as main transcript	c.4786G>T	p.Val1596Phe	missense_variant, splice_region_variant	33/33			ENSP00000509841

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000461

AC:

115

AN:

249420

Hom.:

AF XY:

0.000369

AC XY:

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.000290

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:

0.0000177

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.000190

AC:

278

AN:

1461494

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

116

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.00708

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.00173

AC:

263

AN:

152304

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00611

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000211

Hom.:

Bravo

AF:

0.00198

ESP6500AA

AF:

0.00339

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000488

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Nov 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.70

M_CAP

Benign

0.029

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.22

Sift

Benign

0.079

Sift4G

Benign

0.23

Polyphen

0.83

Vest4

0.23

MVP

0.90

MPC

0.14

ClinPred

0.011

GERP RS

3.4

Varity_R

0.087

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.85

dbscSNV1_RF

Pathogenic

0.74

SpliceAI score (max)

0.69

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.69

Position offset: 0

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