chrX-132386753-T-C

Variant names:

• chrX-132386753-T-C
• rs1936119359
• NM_001386889.1:c.830A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001386889.1(MBNL3):​c.830A>G​(p.Asn277Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000082 in 1,097,628 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000082 (0 hom. 4 hem.)
• Consequence: MBNL3 NM_001386889.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25425327).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

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.830A>G	p.Asn277Ser	missense	Exon 6 of 9	NP_001373818.1	Q9NUK0-1
	MBNL3	NM_001386891.1		c.830A>G	p.Asn277Ser	missense	Exon 6 of 10	NP_001373820.1
	MBNL3	NM_001386892.1		c.830A>G	p.Asn277Ser	missense	Exon 6 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.830A>G	p.Asn277Ser	missense	Exon 6 of 9	ENSP00000359890.3	Q9NUK0-1
	MBNL3	ENST00000538204.6	TSL:1	c.680A>G	p.Asn227Ser	missense	Exon 5 of 7	ENSP00000439618.1	Q9NUK0-4
	MBNL3	ENST00000370844.5	TSL:1	c.542A>G	p.Asn181Ser	missense	Exon 6 of 9	ENSP00000359881.1	Q9NUK0-5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000820 AC: 9 AN: 1097628 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 4 AN XY: 363144

African (AFR) AF: 0.00 AC: 0 AN: 26388

American (AMR) AF: 0.0000852 AC: 3 AN: 35193

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54123

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3852

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 841911

Other (OTH) AF: 0.0000434 AC: 2 AN: 46047

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.058
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.5
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.082
Sift	Benign	0.075	T
Sift4G	Benign	0.16	T
Polyphen		0.55	P
Vest4		0.21
MutPred		0.26		Gain of glycosylation at N277 (P = 0.0042)
MVP		0.57
MPC		0.31
ClinPred		0.86	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.62
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1936119359; hg19: chrX-131520781;