chr13-97391324-A-C

Variant names:

• chr13-97391324-A-C
• rs1378507346
• NM_001382683.1:c.1051A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2 PM4 BP6_Moderate

The NM_001382686.1(MBNL2):​c.1061A>C​(p.Ter354Serext*?) variant causes a stop lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,205,370 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: MBNL2 NM_001382686.1 stop_lost, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.36
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001382686.1 Downstream stopcodon found after 620 codons.
• BP6: Variant 13-97391324-A-C is Benign according to our data. Variant chr13-97391324-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3543869.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382686.1. 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.1051A>C	p.Asn351His	missense splice_region	Exon 9 of 9	NP_001369612.1	A0A7P0T9I3
	MBNL2	NM_001382671.1		c.1015A>C	p.Asn339His	missense splice_region	Exon 8 of 8	NP_001369600.1	A0A994J509
	MBNL2	NM_001382672.1		c.1015A>C	p.Asn339His	missense splice_region	Exon 8 of 8	NP_001369601.1	A0A994J509

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL2	ENST00000679496.1	MANE Select	c.1051A>C	p.Asn351His	missense splice_region	Exon 9 of 9	ENSP00000505596.1	A0A7P0T9I3
	MBNL2	ENST00000376673.8	TSL:1	c.997A>C	p.Asn333His	missense splice_region	Exon 8 of 8	ENSP00000365861.3	Q5VZF2-1
	MBNL2	ENST00000343600.9	TSL:1	c.961A>C	p.Asn321His	missense splice_region	Exon 7 of 7	ENSP00000344214.4	Q5VZF2-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247468 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: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000332 AC: 4 AN: 1205370 Hom.: 0 Cov.: 18 AF XY: 0.00000327 AC XY: 2 AN XY: 611948

African (AFR) AF: 0.00 AC: 0 AN: 28462

American (AMR) AF: 0.00 AC: 0 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24456

East Asian (EAS) AF: 0.00 AC: 0 AN: 38302

South Asian (SAS) AF: 0.00 AC: 0 AN: 80760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5288

European-Non Finnish (NFE) AF: 0.00000455 AC: 4 AN: 879082

Other (OTH) AF: 0.00 AC: 0 AN: 51852

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000469 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.055
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.083	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.46	N
PhyloP100		2.4
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.062
Sift	Benign	0.39	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.27		Gain of catalytic residue at E335 (P = 0.0102)
MVP		0.86
ClinPred		0.22	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.14
Mutation Taster		=85/15	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: rs1378507346; hg19: chr13-98043578;