NM_001376819.1:c.-790+11725T>C

Variant names:

• chr3-152256165-T-C
• rs323622
• NM_001376819.1:c.-790+11725T>C

Variant summary

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

The NM_001376819.1(MBNL1):​c.-790+11725T>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MBNL1 NM_001376819.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 7 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]

MBNL1-AS1 (HGNC:44584): (MBNL1 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=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBNL1	NM_001376819.1	c.-790+11725T>C		intron_variant	Intron 2 of 12		NP_001363748.1
MBNL1	NM_001387781.1	c.-790+11725T>C		intron_variant	Intron 2 of 11		NP_001374710.1
MBNL1	NM_001387785.1	c.-790+11725T>C		intron_variant	Intron 2 of 11		NP_001374714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBNL1	ENST00000477171.1	n.333+11725T>C		intron_variant	Intron 2 of 2	3
MBNL1-AS1	ENST00000669594.1	n.292-9261A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.76
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs323622; hg19: chr3-151973954;