Variant 12-109401121-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001101421.4(MYO1H):c.599G>T(p.Ser200Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00354 in 1,613,944 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 17 hom. )

Consequence

MYO1H
NM_001101421.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.49

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017060041).

BP6

Variant 12-109401121-G-T is Benign according to our data. Variant chr12-109401121-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 717107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYO1H	NM_001101421.4 linkuse as main transcript	c.599G>T	p.Ser200Ile	missense_variant	6/32	ENST00000310903.10
MYO1H	XM_011538223.3 linkuse as main transcript	c.551G>T	p.Ser184Ile	missense_variant	7/34
MYO1H	XM_047428738.1 linkuse as main transcript	c.551G>T	p.Ser184Ile	missense_variant	5/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1H	ENST00000310903.10 linkuse as main transcript	c.599G>T	p.Ser200Ile	missense_variant	6/32	5	NM_001101421.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00207

AC:

315

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00216

AC:

537

AN:

249032

Hom.:

AF XY:

0.00216

AC XY:

292

AN XY:

135082

show subpopulations

Gnomad AFR exome

AF:

0.000711

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00666

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.00309

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00369

AC:

5398

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

2570

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00777

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00102

Gnomad4 FIN exome

AF:

0.000824

Gnomad4 NFE exome

AF:

0.00431

Gnomad4 OTH exome

AF:

0.00308

GnomAD4 genome

AF:

0.00207

AC:

315

AN:

152296

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00337

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00331

Hom.:

Bravo

AF:

0.00212

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000503

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00211

AC:

255

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00308

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	MYO1H: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.017

T;T

MetaSVM

Uncertain

0.50

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

0.94

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.4

.;D

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0010

D;D

Vest4

0.63

MVP

0.86

MPC

0.43

ClinPred

0.042

GERP RS

4.5

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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