Variant 12-109404049-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001101421.4(MYO1H):c.818C>G(p.Ser273Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,613,562 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 183 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 169 hom. )

Consequence

MYO1H
NM_001101421.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.90

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031850636).

BP6

Variant 12-109404049-C-G is Benign according to our data. Variant chr12-109404049-C-G is described in ClinVar as [Benign]. Clinvar id is 768581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYO1H	NM_001101421.4 linkuse as main transcript	c.818C>G	p.Ser273Cys	missense_variant	7/32	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3 linkuse as main transcript	c.770C>G	p.Ser257Cys	missense_variant	8/34		XP_011536525.1
MYO1H	XM_047428738.1 linkuse as main transcript	c.770C>G	p.Ser257Cys	missense_variant	6/31		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10 linkuse as main transcript	c.818C>G	p.Ser273Cys	missense_variant	7/32	5	NM_001101421.4	ENSP00000439182	P1
MYO1H	ENST00000542883.1 linkuse as main transcript	n.148C>G		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.0276

AC:

4203

AN:

152090

Hom.:

181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0953

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.00717

AC:

1783

AN:

248518

Hom.:

AF XY:

0.00531

AC XY:

716

AN XY:

134836

show subpopulations

Gnomad AFR exome

AF:

0.0984

Gnomad AMR exome

AF:

0.00532

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000461

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00304

AC:

4439

AN:

1461356

Hom.:

169

Cov.:

AF XY:

0.00262

AC XY:

1904

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0977

Gnomad4 AMR exome

AF:

0.00580

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000348

Gnomad4 OTH exome

AF:

0.00754

GnomAD4 genome

AF:

0.0277

AC:

4215

AN:

152206

Hom.:

183

Cov.:

AF XY:

0.0259

AC XY:

1929

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0954

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00843

Hom.:

Bravo

AF:

0.0312

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0949

AC:

359

ESP6500EA

AF:

0.000486

AC:

ExAC

AF:

0.00913

AC:

1103

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000535

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.3

.;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.015

D;D

Vest4

0.40

MVP

0.69

MPC

0.37

ClinPred

0.047

GERP RS

4.8

gMVP

0.27

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