NM_021038.5:c.785C>T

Variant names:

• chr3-152445517-C-T
• NM_021038.5:c.785C>T

Variant summary

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

The NM_021038.5(MBNL1):​c.785C>T​(p.Ala262Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBNL1 NM_021038.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

Genes affected

MBNL1 (HGNC:6923): (muscleblind like splicing regulator 1) This gene encodes a member of the muscleblind protein family which was initially described in Drosophila melanogaster. The encoded protein is 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. Mice lacking this gene exhibited muscle abnormalities and cataracts. Several alternatively spliced transcript variants have been described but the full-length natures of only some have been determined. The different isoforms are thought to have different binding specificities and/or splicing activities. [provided by RefSeq, Sep 2015]

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=0.2899303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021038.5. 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
	MBNL1	NM_021038.5	MANE Select	c.785C>T	p.Ala262Val	missense	Exon 5 of 10	NP_066368.2
	MBNL1	NM_001376818.1		c.878C>T	p.Ala293Val	missense	Exon 6 of 12	NP_001363747.1
	MBNL1	NM_001376819.1		c.878C>T	p.Ala293Val	missense	Exon 7 of 13	NP_001363748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL1	ENST00000324210.10	TSL:1 MANE Select	c.785C>T	p.Ala262Val	missense	Exon 5 of 10	ENSP00000319429.5	Q9NR56-5
	MBNL1	ENST00000463374.5	TSL:1	c.785C>T	p.Ala262Val	missense	Exon 4 of 9	ENSP00000418108.1	Q9NR56-1
	MBNL1	ENST00000355460.6	TSL:1	c.785C>T	p.Ala262Val	missense	Exon 5 of 9	ENSP00000347637.2	Q9NR56-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	0.21
BayesDel_addAF	Benign	-0.0043	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	0.063
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.18
Sift	Benign	0.044	D
Sift4G	Benign	0.14	T
Polyphen		0.18	B
Vest4		0.57
MutPred		0.37		Gain of catalytic residue at A262 (P = 0.0145)
MVP		0.36
MPC		2.1
ClinPred		0.90	D
GERP RS		5.4
Varity_R		0.35
gMVP		0.68
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

hg19: chr3-152163306;