17-32659167-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015194.3(MYO1D):c.2293C>T(p.Pro765Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,614,138 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 19 hom. )

Consequence

MYO1D
NM_015194.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.97

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:

ENSG00000264458 (HGNC:58309):

ENSG00000264458 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=0.008619487).

BP6

Variant 17-32659167-G-A is Benign according to our data. Variant chr17-32659167-G-A is described in ClinVar as [Benign]. Clinvar id is 710462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00164 (2398/1461892) while in subpopulation MID AF= 0.0232 (134/5766). AF 95% confidence interval is 0.02. There are 19 homozygotes in gnomad4_exome. There are 1331 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1D	NM_015194.3 link	c.2293C>T	p.Pro765Ser	missense_variant	Exon 17 of 22	ENST00000318217.10	NP_056009.1	O94832Q8N618

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1D	ENST00000318217.10 link	c.2293C>T	p.Pro765Ser	missense_variant	Exon 17 of 22	1	NM_015194.3	ENSP00000324527.5		O94832

Frequencies

GnomAD3 genomes

AF:

0.00405

AC:

616

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00244

AC:

613

AN:

251422

Hom.:

AF XY:

0.00262

AC XY:

356

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0129

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00568

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00164

AC:

2398

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1331

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0136

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.000803

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00601

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000936

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00404

AC:

615

AN:

152246

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00222

Hom.:

Bravo

AF:

0.00490

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0136

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00276

AC:

335

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYO1D: BS1, BS2 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0086

T;T;T

MetaSVM

Uncertain

0.35

MutationAssessor

Uncertain

2.3

M;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-4.8

D;.;.

REVEL

Uncertain

0.55

Sift

Benign

0.13

T;.;.

Sift4G

Benign

0.21

T;T;T

Polyphen

0.78

P;.;.

Vest4

0.55

MVP

0.93

MPC

0.43

ClinPred

0.039

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.17

gMVP

0.68

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