Variant 3-152300313-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_021038.5(MBNL1):c.120G>A(p.Ser40=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,613,936 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.013 ( 15 hom., cov: 32)

Exomes 𝑓: 0.019 ( 320 hom. )

Consequence

MBNL1
NM_021038.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

MBNL1 (HGNC:6923): (muscleblind like splicing regulator 1) This gene encodes a member of the muscleblind protein family which was initially described in Drosophila melanogaster. The encoded protein is a C3H-type zinc finger protein that modulates alternative splicing of pre-mRNAs. Muscleblind proteins bind specifically to expanded dsCUG RNA but not to normal size CUG repeats and may thereby play a role in the pathophysiology of myotonic dystrophy. Mice lacking this gene exhibited muscle abnormalities and cataracts. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. The different isoforms are thought to have different binding specificities and/or splicing activities. [provided by RefSeq, Sep 2015]

MBNL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-152300313-G-A is Benign according to our data. Variant chr3-152300313-G-A is described in ClinVar as [Benign]. Clinvar id is 3055807.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0127 (1935/152246) while in subpopulation NFE AF= 0.0203 (1384/68012). AF 95% confidence interval is 0.0195. There are 15 homozygotes in gnomad4. There are 886 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1935 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBNL1	NM_021038.5 linkuse as main transcript	c.120G>A	p.Ser40=	synonymous_variant	2/10	ENST00000324210.10	NP_066368.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBNL1	ENST00000324210.10 linkuse as main transcript	c.120G>A	p.Ser40=	synonymous_variant	2/10	1	NM_021038.5	ENSP00000319429	A1	Q9NR56-5

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1935

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0188

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0203

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0125

AC:

3153

AN:

251392

Hom.:

AF XY:

0.0127

AC XY:

1728

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00258

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.00430

Gnomad NFE exome

AF:

0.0212

Gnomad OTH exome

AF:

0.0173

GnomAD4 exome

AF:

0.0191

AC:

27906

AN:

1461690

Hom.:

320

Cov.:

AF XY:

0.0187

AC XY:

13567

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00176

Gnomad4 FIN exome

AF:

0.00519

Gnomad4 NFE exome

AF:

0.0231

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0127

AC:

1935

AN:

152246

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

886

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00361

Gnomad4 AMR

AF:

0.0188

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00377

Gnomad4 NFE

AF:

0.0203

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0168

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0190

EpiControl

AF:

0.0232

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MBNL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.78

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