Variant X-132386816-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001386889.1(MBNL3):c.772-5C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,204,860 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000019 ( 0 hom. 8 hem. )

Consequence

MBNL3
NM_001386889.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001937

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.773

Variant links:

Genes affected

MBNL3 (HGNC:20564): (muscleblind like splicing regulator 3) This gene encodes a member of the muscleblind-like family of proteins. The encoded protein may function in regulation of alternative splicing and may play a role in the pathophysiology of myotonic dystrophy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Dec 2009]

MBNL3 links:

RAP2C-AS1 (HGNC:40957): (RAP2C antisense RNA 1)

RAP2C-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-132386816-G-T is Benign according to our data. Variant chrX-132386816-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043463.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBNL3	NM_001386889.1 linkuse as main transcript	c.772-5C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370853.8	NP_001373818.1
RAP2C-AS1	NR_110410.1 linkuse as main transcript	n.424-42997G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBNL3	ENST00000370853.8 linkuse as main transcript	c.772-5C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001386889.1	ENSP00000359890	A1	Q9NUK0-1
RAP2C-AS1	ENST00000441399.3 linkuse as main transcript	n.722-42997G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000367

AC:

AN:

108936

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33120

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00202

GnomAD3 exomes

AF:

0.0000499

AC:

AN:

180358

Hom.:

AF XY:

0.0000753

AC XY:

AN XY:

66422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.000211

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1095870

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

361484

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000148

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000714

Gnomad4 OTH exome

AF:

0.0000870

GnomAD4 genome

AF:

0.0000367

AC:

AN:

108990

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33184

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00199

Bravo

AF:

0.000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MBNL3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 24, 2019

This variant is classified as likely 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

-0.85

CADD

Benign

0.82

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.010

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