rs17659179

Positions:

chr18-49984743-C-A

Variant summary

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

The NM_001080467.3(MYO5B):c.921G>T(p.Lys307Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 1,612,904 control chromosomes in the GnomAD database, including 2,840 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 0.046 ( 192 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2648 hom. )

Consequence

MYO5B
NM_001080467.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.13

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=0.015074998).

BP6

Variant 18-49984743-C-A is Benign according to our data. Variant chr18-49984743-C-A is described in ClinVar as [Benign]. Clinvar id is 327075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49984743-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO5B	NM_001080467.3 linkuse as main transcript	c.921G>T	p.Lys307Asn	missense_variant	8/40	ENST00000285039.12	NP_001073936.1	Q9ULV0-1Q7Z7A5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12 linkuse as main transcript	c.921G>T	p.Lys307Asn	missense_variant	8/40	1	NM_001080467.3	ENSP00000285039.6		Q9ULV0-1
MYO5B	ENST00000697219.1 linkuse as main transcript	c.717G>T	p.Lys239Asn	missense_variant	6/38			ENSP00000513188.1		A0A8V8TM52

Frequencies

GnomAD3 genomes

AF:

0.0462

AC:

7032

AN:

152134

Hom.:

192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.0532

Gnomad ASJ

AF:

0.0407

Gnomad EAS

AF:

0.00926

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.0536

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0635

Gnomad OTH

AF:

0.0450

GnomAD3 exomes

AF:

0.0515

AC:

12845

AN:

249500

Hom.:

382

AF XY:

0.0514

AC XY:

6957

AN XY:

135360

show subpopulations

Gnomad AFR exome

AF:

0.0197

Gnomad AMR exome

AF:

0.0670

Gnomad ASJ exome

AF:

0.0475

Gnomad EAS exome

AF:

0.00879

Gnomad SAS exome

AF:

0.0347

Gnomad FIN exome

AF:

0.0491

Gnomad NFE exome

AF:

0.0633

Gnomad OTH exome

AF:

0.0505

GnomAD4 exome

AF:

0.0576

AC:

84171

AN:

1460652

Hom.:

2648

Cov.:

AF XY:

0.0569

AC XY:

41341

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.0636

Gnomad4 ASJ exome

AF:

0.0475

Gnomad4 EAS exome

AF:

0.00544

Gnomad4 SAS exome

AF:

0.0330

Gnomad4 FIN exome

AF:

0.0531

Gnomad4 NFE exome

AF:

0.0634

Gnomad4 OTH exome

AF:

0.0479

GnomAD4 genome

AF:

0.0462

AC:

7031

AN:

152252

Hom.:

192

Cov.:

AF XY:

0.0453

AC XY:

3375

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.0532

Gnomad4 ASJ

AF:

0.0407

Gnomad4 EAS

AF:

0.00928

Gnomad4 SAS

AF:

0.0268

Gnomad4 FIN

AF:

0.0536

Gnomad4 NFE

AF:

0.0635

Gnomad4 OTH

AF:

0.0441

Alfa

AF:

0.0575

Hom.:

530

Bravo

AF:

0.0446

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.0577

AC:

482

ExAC

AF:

0.0511

AC:

6174

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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: MAF -

Congenital microvillous atrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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

Benign

0.25

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.046

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.84

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.015

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.85

REVEL

Uncertain

0.32

Sift

Benign

0.14

Sift4G

Benign

0.19

Polyphen

0.0040

Vest4

0.59

MutPred

0.23

Loss of ubiquitination at K307 (P = 0.0297);

MPC

0.69

ClinPred

0.013

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.55

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