rs1815930

Variant names:

Variant summary

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

The NM_001080467.3(MYO5B):c.376A>G(p.Thr126Ala) variant causes a missense change. The variant allele was found at a frequency of 0.996 in 1,614,124 control chromosomes in the GnomAD database, including 800,410 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.98 ( 72866 hom., cov: 31)

Exomes 𝑓: 1.0 ( 727544 hom. )

Consequence

MYO5B
NM_001080467.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 6.18

Variant links:

Genes affected

MYO5B (HGNC:7603): (myosin VB) The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

MYO5B 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=9.517018E-7).

BP6

Variant 18-50036929-T-C is Benign according to our data. Variant chr18-50036929-T-C is described in ClinVar as [Benign]. Clinvar id is 327087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-50036929-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.376A>G	p.Thr126Ala	missense_variant	Exon 4 of 40	ENST00000285039.12	NP_001073936.1	Q9ULV0-1Q7Z7A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO5B	ENST00000285039.12 link	c.376A>G	p.Thr126Ala	missense_variant	Exon 4 of 40	1	NM_001080467.3	ENSP00000285039.6	Q9ULV0-1
MYO5B	ENST00000697219.1 link	c.172A>G	p.Thr58Ala	missense_variant	Exon 2 of 38			ENSP00000513188.1	A0A8V8TM52
MYO5B	ENST00000697221.1 link	n.747A>G		non_coding_transcript_exon_variant	Exon 4 of 5

Frequencies

GnomAD3 genomes

AF:

0.978

AC:

148738

AN:

152122

Hom.:

72810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.923

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.992

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.983

GnomAD3 exomes

AF:

0.994

AC:

248169

AN:

249558

Hom.:

123437

AF XY:

0.996

AC XY:

134827

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.923

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.999

GnomAD4 exome

AF:

0.998

AC:

1458388

AN:

1461884

Hom.:

727544

Cov.:

AF XY:

0.998

AC XY:

725743

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.922

Gnomad4 AMR exome

AF:

0.996

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.995

GnomAD4 genome

AF:

0.978

AC:

148852

AN:

152240

Hom.:

72866

Cov.:

AF XY:

0.979

AC XY:

72837

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.923

Gnomad4 AMR

AF:

0.992

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.983

Alfa

AF:

0.995

Hom.:

117746

Bravo

AF:

0.975

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

1.00

AC:

3854

ESP6500AA

AF:

0.931

AC:

3738

ESP6500EA

AF:

0.999

AC:

8352

ExAC

AF:

0.993

AC:

120012

Asia WGS

AF:

0.997

AC:

3467

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

1.00

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital microvillous atrophy

Benign:4

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2019

GeneDx

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

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.036

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.13

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.55

MetaRNN

Benign

9.5e-7

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.2

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

2.8

REVEL

Uncertain

0.35

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.095

MPC

0.14

ClinPred

0.0037

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.13

gMVP

0.33

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