Variant 12-109393391-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001101421.4(MYO1H):c.235G>A(p.Val79Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,589,594 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

MYO1H
NM_001101421.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.374

Variant links:

Genes affected

MYO1H (HGNC:13879): (myosin IH) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

MYO1H links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040190667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYO1H	NM_001101421.4 linkuse as main transcript	c.235G>A	p.Val79Met	missense_variant	3/32	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3 linkuse as main transcript	c.187G>A	p.Val63Met	missense_variant	4/34		XP_011536525.1
MYO1H	XM_047428738.1 linkuse as main transcript	c.187G>A	p.Val63Met	missense_variant	2/31		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10 linkuse as main transcript	c.235G>A	p.Val79Met	missense_variant	3/32	5	NM_001101421.4	ENSP00000439182	P1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000704

AC:

AN:

212960

Hom.:

AF XY:

0.0000702

AC XY:

AN XY:

113988

show subpopulations

Gnomad AFR exome

AF:

0.0000777

Gnomad AMR exome

AF:

0.0000658

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000767

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.000367

GnomAD4 exome

AF:

0.000102

AC:

147

AN:

1437338

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

712348

show subpopulations

Gnomad4 AFR exome

AF:

0.000272

Gnomad4 AMR exome

AF:

0.000122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000972

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000828

Gnomad4 OTH exome

AF:

0.000252

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000747

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 06, 2022

The c.187G>A (p.V63M) alteration is located in exon 2 (coding exon 2) of the MYO1H gene. This alteration results from a G to A substitution at nucleotide position 187, causing the valine (V) at amino acid position 63 to be replaced by a methionine (M). 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

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.46

CADD

Benign

4.7

DANN

Benign

0.90

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.10

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.50

.;N

REVEL

Benign

0.19

Sift

Benign

0.071

.;T

Sift4G

Uncertain

0.046

D;T

Vest4

0.21

MVP

0.26

MPC

0.082

ClinPred

0.017

GERP RS

-9.9

gMVP

0.37

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