chrX-132386816-G-C

Variant names:

• chrX-132386816-G-C
• rs185006165
• NM_001386889.1:c.772-5C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001386889.1(MBNL3):​c.772-5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,095,871 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts 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: 21)
  • Exomes 𝑓: 0.0000064 (0 hom. 1 hem.)
• Consequence: MBNL3 NM_001386889.1 splice_region, intron
• Scores: Splicing: ADA: 0.0002185
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

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.772-5C>G		splice_region intron	N/A	NP_001373818.1	Q9NUK0-1
	MBNL3	NM_001386891.1		c.772-5C>G		splice_region intron	N/A	NP_001373820.1
	MBNL3	NM_001386892.1		c.772-5C>G		splice_region intron	N/A	NP_001373821.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBNL3	ENST00000370853.8	TSL:1 MANE Select	c.772-5C>G		splice_region intron	N/A	ENSP00000359890.3	Q9NUK0-1
	MBNL3	ENST00000370839.7	TSL:1	c.772-110C>G		intron	N/A	ENSP00000359876.3	Q9NUK0-2
	MBNL3	ENST00000538204.6	TSL:1	c.622-5C>G		splice_region intron	N/A	ENSP00000439618.1	Q9NUK0-4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 180358 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: 0.000145

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1095871 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1 AN XY: 361485

African (AFR) AF: 0.00 AC: 0 AN: 26347

American (AMR) AF: 0.00 AC: 0 AN: 35179

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19348

East Asian (EAS) AF: 0.0000663 AC: 2 AN: 30185

South Asian (SAS) AF: 0.00 AC: 0 AN: 53981

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40465

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3832

European-Non Finnish (NFE) AF: 0.00000476 AC: 4 AN: 840543

Other (OTH) AF: 0.0000217 AC: 1 AN: 45991

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.37
PhyloP100		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00022
dbscSNV1_RF	Benign	0.024
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: rs185006165; hg19: chrX-131520844;