rs1942418

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.3962G>A(p.Gly1321Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0723 in 1,613,512 control chromosomes in the GnomAD database, including 9,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 955 hom., cov: 33)

Exomes 𝑓: 0.072 ( 8270 hom. )

Consequence

MYO5B
NM_001080467.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.59

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=0.0016974807).

BP6

Variant 18-49856873-C-T is Benign according to our data. Variant chr18-49856873-C-T is described in ClinVar as [Benign]. Clinvar id is 327017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49856873-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3 link	c.3962G>A	p.Gly1321Glu	missense_variant	Exon 30 of 40	ENST00000285039.12	NP_001073936.1	Q9ULV0-1Q7Z7A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12 link	c.3962G>A	p.Gly1321Glu	missense_variant	Exon 30 of 40	1	NM_001080467.3	ENSP00000285039.6		Q9ULV0-1

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12062

AN:

152190

Hom.:

946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0562

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0894

GnomAD3 exomes

AF:

0.121

AC:

30124

AN:

249452

Hom.:

3953

AF XY:

0.108

AC XY:

14647

AN XY:

135344

show subpopulations

Gnomad AFR exome

AF:

0.0548

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.0448

Gnomad EAS exome

AF:

0.293

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0578

Gnomad NFE exome

AF:

0.0478

Gnomad OTH exome

AF:

0.0933

GnomAD4 exome

AF:

0.0715

AC:

104540

AN:

1461204

Hom.:

8270

Cov.:

AF XY:

0.0710

AC XY:

51598

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.0553

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.0432

Gnomad4 EAS exome

AF:

0.361

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0569

Gnomad4 NFE exome

AF:

0.0485

Gnomad4 OTH exome

AF:

0.0755

GnomAD4 genome

AF:

0.0794

AC:

12094

AN:

152308

Hom.:

955

Cov.:

AF XY:

0.0840

AC XY:

6257

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0547

Gnomad4 AMR

AF:

0.230

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.296

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0562

Gnomad4 NFE

AF:

0.0478

Gnomad4 OTH

AF:

0.0903

Alfa

AF:

0.0601

Hom.:

1349

Bravo

AF:

0.0957

TwinsUK

AF:

0.0499

AC:

185

ALSPAC

AF:

0.0519

AC:

200

ESP6500AA

AF:

0.0482

AC:

184

ESP6500EA

AF:

0.0517

AC:

427

ExAC

AF:

0.109

AC:

13137

Asia WGS

AF:

0.177

AC:

613

AN:

3478

EpiCase

AF:

0.0492

EpiControl

AF:

0.0483

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

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

- -

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Congenital microvillous atrophy

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.030

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.025

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.43

REVEL

Benign

0.081

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.049

Vest4

0.37

MPC

0.71

ClinPred

0.024

GERP RS

5.3

Varity_R

0.19

gMVP

0.61

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