Variant rs3825393 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.3050T>C(p.Leu1017Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,610,944 control chromosomes in the GnomAD database, including 347,915 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 40130 hom., cov: 32)

Exomes 𝑓: 0.65 ( 307785 hom. )

Consequence

MYO1H
NM_001101421.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0330

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:

ENSG00000255655 (HGNC:):

ENSG00000255655 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=6.0434917E-7).

BP6

Variant 12-109445569-T-C is Benign according to our data. Variant chr12-109445569-T-C is described in ClinVar as [Benign]. Clinvar id is 1267555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1H	NM_001101421.4 link	c.3050T>C	p.Leu1017Pro	missense_variant	31/32	ENST00000310903.10	NP_001094891.4	B4DNW6
MYO1H	XM_011538223.3 link	c.3068T>C	p.Leu1023Pro	missense_variant	33/34		XP_011536525.1
MYO1H	XM_047428738.1 link	c.3002T>C	p.Leu1001Pro	missense_variant	30/31		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYO1H	ENST00000310903.10 link	c.3050T>C	p.Leu1017Pro	missense_variant	31/32	5	NM_001101421.4	ENSP00000439182.2	A0A140TA25
ENSG00000255655	ENST00000539987.1 link	n.444A>G		non_coding_transcript_exon_variant	2/2	3
MYO1H	ENST00000542268.5 link	n.850T>C		non_coding_transcript_exon_variant	8/9	2
MYO1H	ENST00000543960.1 link	n.314T>C		non_coding_transcript_exon_variant	4/6	4		ENSP00000474025.1	S4R387

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108166

AN:

151982

Hom.:

40072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.931

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.692

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.650

Gnomad OTH

AF:

0.700

GnomAD3 exomes

AF:

0.644

AC:

159137

AN:

247116

Hom.:

52658

AF XY:

0.649

AC XY:

86954

AN XY:

134028

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.528

Gnomad ASJ exome

AF:

0.681

Gnomad EAS exome

AF:

0.505

Gnomad SAS exome

AF:

0.712

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.645

AC:

941597

AN:

1458844

Hom.:

307785

Cov.:

AF XY:

0.648

AC XY:

470419

AN XY:

725596

show subpopulations

Gnomad4 AFR exome

AF:

0.943

Gnomad4 AMR exome

AF:

0.542

Gnomad4 ASJ exome

AF:

0.674

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.711

Gnomad4 FIN exome

AF:

0.558

Gnomad4 NFE exome

AF:

0.644

Gnomad4 OTH exome

AF:

0.653

GnomAD4 genome

AF:

0.712

AC:

108281

AN:

152100

Hom.:

40130

Cov.:

AF XY:

0.702

AC XY:

52156

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.931

Gnomad4 AMR

AF:

0.591

Gnomad4 ASJ

AF:

0.674

Gnomad4 EAS

AF:

0.502

Gnomad4 SAS

AF:

0.692

Gnomad4 FIN

AF:

0.550

Gnomad4 NFE

AF:

0.650

Gnomad4 OTH

AF:

0.700

Alfa

AF:

0.656

Hom.:

71855

Bravo

AF:

0.724

TwinsUK

AF:

0.646

AC:

2395

ALSPAC

AF:

0.633

AC:

2441

ESP6500AA

AF:

0.920

AC:

3399

ESP6500EA

AF:

0.644

AC:

5268

ExAC

AF:

0.658

AC:

79488

Asia WGS

AF:

0.606

AC:

2107

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 18, 2020	This variant is associated with the following publications: (PMID: 29986156) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.62

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.0071

T;T

MetaRNN

Benign

6.0e-7

T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.28

REVEL

Benign

0.030

Sift4G

Benign

0.43

T;T

Vest4

0.028

MPC

0.13

ClinPred

0.00085

GERP RS

2.8

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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