NM_001386889.1:c.301C>A

Variant names:

• chrX-132406269-G-T
• NM_001386889.1:c.301C>A

Variant summary

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

The NM_001386889.1(MBNL3):​c.301C>A​(p.Gln101Lys) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MBNL3 NM_001386889.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

MBNL3 (HGNC:20564): (muscleblind like splicing regulator 3) This gene encodes a member of the muscleblind-like family of proteins. The encoded protein may function in regulation of alternative splicing and may play a role in the pathophysiology of myotonic dystrophy. Alternatively spliced transcript variants have been described. [provided by RefSeq, Dec 2009]

RAP2C-AS1 (HGNC:40957): (RAP2C antisense RNA 1)

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=0.41111475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386889.1. 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
	MBNL3	NM_001386889.1	MANE Select	c.301C>A	p.Gln101Lys	missense	Exon 3 of 9	NP_001373818.1	Q9NUK0-1
	MBNL3	NM_001386891.1		c.301C>A	p.Gln101Lys	missense	Exon 3 of 10	NP_001373820.1
	MBNL3	NM_001386892.1		c.301C>A	p.Gln101Lys	missense	Exon 3 of 10	NP_001373821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL3	ENST00000370853.8	TSL:1 MANE Select	c.301C>A	p.Gln101Lys	missense	Exon 3 of 9	ENSP00000359890.3	Q9NUK0-1
	MBNL3	ENST00000370839.7	TSL:1	c.301C>A	p.Gln101Lys	missense	Exon 2 of 9	ENSP00000359876.3	Q9NUK0-2
	MBNL3	ENST00000538204.6	TSL:1	c.151C>A	p.Gln51Lys	missense	Exon 2 of 7	ENSP00000439618.1	Q9NUK0-4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	MBNL3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		10
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.012	D
Polyphen		0.48	P
Vest4		0.59
MutPred		0.33		Gain of ubiquitination at Q101 (P = 0.0219)
MVP		0.59
MPC		0.83
ClinPred		0.95	D
GERP RS		5.8
Varity_R		0.50
gMVP		0.92
Mutation Taster		=35/65	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

hg19: chrX-131540297;