rs576822266

Variant names:

• chr13-97346855-C-A
• rs576822266
• NM_001382683.1:c.592C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-97346855-C-A
• chr13-97346855-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001382683.1(MBNL2):​c.592C>A​(p.Arg198Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R198C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBNL2 NM_001382683.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.89
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

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.592C>A	p.Arg198Ser	missense	Exon 5 of 9	NP_001369612.1	A0A7P0T9I3
	MBNL2	NM_001382669.1		c.592C>A	p.Arg198Ser	missense	Exon 5 of 10	NP_001369598.1	A0A994J506
	MBNL2	NM_001382670.1		c.592C>A	p.Arg198Ser	missense	Exon 5 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.592C>A	p.Arg198Ser	missense	Exon 5 of 9	ENSP00000505596.1	A0A7P0T9I3
	MBNL2	ENST00000376673.8	TSL:1	c.592C>A	p.Arg198Ser	missense	Exon 5 of 8	ENSP00000365861.3	Q5VZF2-1
	MBNL2	ENST00000345429.10	TSL:1	c.592C>A	p.Arg198Ser	missense	Exon 5 of 9	ENSP00000267287.7	Q5VZF2-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251172 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.77
MutPred		0.76		Gain of catalytic residue at A200 (P = 0.0017)
MVP		0.53
MPC		2.1
ClinPred		1.0	D
GERP RS		6.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.90
gMVP		0.95
Mutation Taster		=0/100	disease causing

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: rs576822266; hg19: chr13-97999109;