Variant chr17-32659148-C-T 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_015194.3(MYO1D):c.2312G>A(p.Arg771His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,614,176 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 123 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 126 hom. )

Consequence

MYO1D
NM_015194.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

MYO1D (HGNC:7598): (myosin ID) Enables protein domain specific binding activity. Predicted to be involved in actin filament organization; early endosome to recycling endosome transport; and vesicle transport along actin filament. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MYO1D links:

(HGNC:):

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=0.0021068454).

BP6

Variant 17-32659148-C-T is Benign according to our data. Variant chr17-32659148-C-T is described in ClinVar as [Benign]. Clinvar id is 781363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1D	NM_015194.3 linkuse as main transcript	c.2312G>A	p.Arg771His	missense_variant	17/22	ENST00000318217.10	NP_056009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1D	ENST00000318217.10 linkuse as main transcript	c.2312G>A	p.Arg771His	missense_variant	17/22	1	NM_015194.3	ENSP00000324527	P1
	ENST00000582272.1 linkuse as main transcript	n.141+26669C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3283

AN:

152176

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00151

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.00723

AC:

1818

AN:

251282

Hom.:

AF XY:

0.00618

AC XY:

839

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.0757

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00591

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.00350

AC:

5115

AN:

1461882

Hom.:

126

Cov.:

AF XY:

0.00349

AC XY:

2537

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0749

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.000803

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00624

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00657

GnomAD4 genome

AF:

0.0217

AC:

3301

AN:

152294

Hom.:

123

Cov.:

AF XY:

0.0210

AC XY:

1567

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0727

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00564

Hom.:

Bravo

AF:

0.0245

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0679

AC:

299

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00853

AC:

1036

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00240

EpiControl

AF:

0.00243

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

T;T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.3

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.64

N;.;.

REVEL

Uncertain

0.30

Sift

Benign

0.23

T;.;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.94

P;.;.

Vest4

0.19

MVP

0.83

MPC

0.34

ClinPred

0.0082

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.030

gMVP

0.43

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