13-97343170-C-G

Variant names:

• chr13-97343170-C-G
• rs369422314
• NM_001382683.1:c.494C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001382683.1(MBNL2):​c.494C>G​(p.Pro165Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P165L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MBNL2 NM_001382683.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382683.1. 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.494C>G	p.Pro165Arg	missense	Exon 4 of 9	NP_001369612.1	A0A7P0T9I3
	MBNL2	NM_001382669.1		c.494C>G	p.Pro165Arg	missense	Exon 4 of 10	NP_001369598.1	A0A994J506
	MBNL2	NM_001382670.1		c.494C>G	p.Pro165Arg	missense	Exon 4 of 10	NP_001369599.1	A0A994J506

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL2	ENST00000679496.1	MANE Select	c.494C>G	p.Pro165Arg	missense	Exon 4 of 9	ENSP00000505596.1	A0A7P0T9I3
	MBNL2	ENST00000376673.8	TSL:1	c.494C>G	p.Pro165Arg	missense	Exon 4 of 8	ENSP00000365861.3	Q5VZF2-1
	MBNL2	ENST00000345429.10	TSL:1	c.494C>G	p.Pro165Arg	missense	Exon 4 of 9	ENSP00000267287.7	Q5VZF2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	0.00029	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.064	T
Polyphen		0.50	P
Vest4		0.68
MutPred		0.37		Gain of catalytic residue at P160 (P = 2e-04)
MVP		0.12
MPC		1.3
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.28
gMVP		0.61
Mutation Taster		=57/43	polymorphism

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: rs369422314; hg19: chr13-97995424;