Variant 12-109393367-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001101421.4(MYO1H):c.211T>C(p.Tyr71His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,585,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

MYO1H
NM_001101421.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYO1H	NM_001101421.4 linkuse as main transcript	c.211T>C	p.Tyr71His	missense_variant	3/32	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3 linkuse as main transcript	c.163T>C	p.Tyr55His	missense_variant	4/34		XP_011536525.1
MYO1H	XM_047428738.1 linkuse as main transcript	c.163T>C	p.Tyr55His	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.211T>C	p.Tyr71His	missense_variant	3/32	5	NM_001101421.4	ENSP00000439182	P1

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151428

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:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000286

AC:

AN:

209472

Hom.:

AF XY:

0.00000893

AC XY:

AN XY:

111924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000333

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:

0.0000547

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000279

AC:

AN:

1434252

Hom.:

Cov.:

AF XY:

0.0000267

AC XY:

AN XY:

710490

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000246

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:

0.0000301

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151428

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73966

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:

0.0000737

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.00000830

AC:

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 14, 2023

The c.163T>C (p.Y55H) alteration is located in exon 2 (coding exon 2) of the MYO1H gene. This alteration results from a T to C substitution at nucleotide position 163, causing the tyrosine (Y) at amino acid position 55 to be replaced by a histidine (H). 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

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Uncertain

0.76

MutationAssessor

Pathogenic

3.3

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.7

.;D

REVEL

Pathogenic

0.92

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.021

D;D

Vest4

0.93

MutPred

0.78

.;Gain of catalytic residue at Q56 (P = 9e-04);

MVP

0.78

MPC

0.14

ClinPred

0.89

GERP RS

4.5

gMVP

0.93

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