chr13-97366474-G-A

Variant names:

• chr13-97366474-G-A
• ENST00000345429.10:c.1010G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001382687.1(MBNL2):​c.959-1G>A variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBNL2 NM_001382687.1 splice_acceptor, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27357435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382687.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL2	NM_001382683.1	MANE Select	c.1048+1303G>A		intron	N/A	NP_001369612.1	A0A7P0T9I3
	MBNL2	NM_001382669.1		c.1064G>A	p.Ser355Asn	missense	Exon 9 of 10	NP_001369598.1	A0A994J506
	MBNL2	NM_001382670.1		c.1064G>A	p.Ser355Asn	missense	Exon 9 of 10	NP_001369599.1	A0A994J506

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL2	ENST00000345429.10	TSL:1	c.1010G>A	p.Ser337Asn	missense	Exon 8 of 9	ENSP00000267287.7	Q5VZF2-2
	MBNL2	ENST00000679496.1	MANE Select	c.1048+1303G>A		intron	N/A	ENSP00000505596.1	A0A7P0T9I3
	MBNL2	ENST00000376673.8	TSL:1	c.994+1303G>A		intron	N/A	ENSP00000365861.3	Q5VZF2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
PhyloP100		7.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.072
Sift	Benign	0.053	T
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.28		Gain of catalytic residue at M335 (P = 0.0022)
MVP		0.48
MPC		0.82
ClinPred		0.71	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

hg19: chr13-98018728;