Variant 18-49823251-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080467.3(MYO5B):c.*3220C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.23 ( 0 hom., cov: 36)

Exomes 𝑓: 0.25 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYO5B
NM_001080467.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.361

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:

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

SNHG22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5B	NM_001080467.3 linkuse as main transcript	c.*3220C>T		3_prime_UTR_variant	40/40	ENST00000285039.12
SNHG22	NR_117096.1 linkuse as main transcript	n.40+9189G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5B	ENST00000285039.12 linkuse as main transcript	c.*3220C>T		3_prime_UTR_variant	40/40	1	NM_001080467.3	P1	Q9ULV0-1
SNHG22	ENST00000589499.1 linkuse as main transcript	n.40+9189G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

9678

AN:

42422

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.223

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.228

AC:

9698

AN:

42470

Hom.:

Cov.:

AF XY:

0.223

AC XY:

4724

AN XY:

21230

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.245

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.296

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital microvillous atrophy

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

1.1

Dann

Benign

0.43

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