rs3826579

Variant summary

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

The NM_001080467.3(MYO5B):c.3591C>T(p.Tyr1197=) variant causes a synonymous change. The variant allele was found at a frequency of 0.22 in 1,613,140 control chromosomes in the GnomAD database, including 41,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4531 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36902 hom. )

Consequence

MYO5B
NM_001080467.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.95

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 (BayesDel_noAF=-0.49).

BP6

Variant 18-49872179-G-A is Benign according to our data. Variant chr18-49872179-G-A is described in ClinVar as [Benign]. Clinvar id is 327025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49872179-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3 linkuse as main transcript	c.3591C>T	p.Tyr1197=	synonymous_variant	27/40	ENST00000285039.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12 linkuse as main transcript	c.3591C>T	p.Tyr1197=	synonymous_variant	27/40	1	NM_001080467.3	P1	Q9ULV0-1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36500

AN:

151886

Hom.:

4523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.198

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.255

AC:

63750

AN:

249532

Hom.:

8886

AF XY:

0.256

AC XY:

34649

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.269

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.226

Gnomad EAS exome

AF:

0.434

Gnomad SAS exome

AF:

0.344

Gnomad FIN exome

AF:

0.258

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.218

AC:

318281

AN:

1461136

Hom.:

36902

Cov.:

AF XY:

0.221

AC XY:

160636

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.339

Gnomad4 FIN exome

AF:

0.258

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.240

AC:

36546

AN:

152004

Hom.:

4531

Cov.:

AF XY:

0.246

AC XY:

18267

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.419

Gnomad4 SAS

AF:

0.341

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.198

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.211

Hom.:

6630

Bravo

AF:

0.240

Asia WGS

AF:

0.362

AC:

1258

AN:

3478

EpiCase

AF:

0.201

EpiControl

AF:

0.201

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital microvillous atrophy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

Cadd

Benign

5.8

Dann

Benign

0.86

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