chr13-97315064-C-T

Variant names:

• chr13-97315064-C-T
• rs9516905
• NM_001382683.1:c.175-19212C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382683.1(MBNL2):​c.175-19212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 151,938 control chromosomes in the GnomAD database, including 2,305 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2305 hom., cov: 32)
• Consequence: MBNL2 NM_001382683.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 2 publications found

Genes affected

MBNL2 (HGNC:16746): (muscleblind like splicing regulator 2) This gene is a member of the muscleblind protein family which was initially described in Drosophila melanogaster. This gene encodes 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. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBNL2	NM_001382683.1	c.175-19212C>T		intron_variant	Intron 2 of 8	ENST00000679496.1	NP_001369612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBNL2	ENST00000679496.1	c.175-19212C>T		intron_variant	Intron 2 of 8		NM_001382683.1	ENSP00000505596.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25532 AN: 151818 Hom.: 2293 Cov.: 32

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25584 AN: 151938 Hom.: 2305 Cov.: 32 AF XY: 0.170 AC XY: 12659 AN XY: 74258

African (AFR) AF: 0.240 AC: 9938 AN: 41404

American (AMR) AF: 0.188 AC: 2877 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3468

East Asian (EAS) AF: 0.151 AC: 781 AN: 5174

South Asian (SAS) AF: 0.185 AC: 889 AN: 4812

European-Finnish (FIN) AF: 0.178 AC: 1876 AN: 10516

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8253 AN: 67974

Other (OTH) AF: 0.154 AC: 324 AN: 2110

Alfa AF: 0.140 Hom.: 1017

Bravo AF: 0.172

Asia WGS AF: 0.199 AC: 690 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.16
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9516905; hg19: chr13-97967318;