chrX-132392333-C-T

Variant names:

• chrX-132392333-C-T
• rs143863668
• NM_001386889.1:c.344G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001386889.1(MBNL3):​c.344G>A​(p.Gly115Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: MBNL3 NM_001386889.1 missense, splice_region
• Scores: Splicing: ADA: 0.00005875
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07747191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBNL3	NM_001386889.1	c.344G>A	p.Gly115Asp	missense_variant, splice_region_variant	Exon 4 of 9	ENST00000370853.8	NP_001373818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBNL3	ENST00000370853.8	c.344G>A	p.Gly115Asp	missense_variant, splice_region_variant	Exon 4 of 9	1	NM_001386889.1	ENSP00000359890.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.89
DEOGEN2	Benign	0.020	.;.;T;T;.;.;.;T;T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	T;T;T;T;T;T;.;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.077	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	.;.;.;L;.;L;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.92	N;N;N;N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.24	T;D;T;T;T;T;D;D;D
Sift4G	Benign	0.52	T;T;T;T;T;T;T;.;.
Polyphen		0.031	B;.;.;B;B;B;.;.;.
Vest4		0.16
MutPred		0.071		.;.;Loss of glycosylation at S116 (P = 0.1624);Loss of glycosylation at S116 (P = 0.1624);.;Loss of glycosylation at S116 (P = 0.1624);.;.;.;
MVP		0.52
MPC		0.51
ClinPred		0.052	T
GERP RS		1.3
Varity_R		0.11
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000059
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs143863668; hg19: chrX-131526361;