2-148489377-T-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001378120.1(MBD5):c.3754-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,614,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001378120.1 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.3754-9T>C | intron_variant | Intron 10 of 13 | ENST00000642680.2 | NP_001365049.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.3754-9T>C | intron_variant | Intron 10 of 13 | NM_001378120.1 | ENSP00000493871.2 |
Frequencies
GnomAD3 genomes AF: 0.000907 AC: 138AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000382 AC: 96AN: 251074Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135754
GnomAD4 exome AF: 0.000172 AC: 252AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.000144 AC XY: 105AN XY: 727208
GnomAD4 genome AF: 0.000906 AC: 138AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000940 AC XY: 70AN XY: 74486
ClinVar
Submissions by phenotype
not specified Benign:3
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Intellectual disability, autosomal dominant 1 Uncertain:1Benign:1
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MBD5 NM_018328 exon 12 c.3055-9T>C: This variant has not been reported in the literature but is present in 0.3% (78/24026) of African individuals in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs370173652). This variant is present in ClinVar (Variation ID:206053). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Although this variant occurs in the splice region, it is not predicted to alter the consensus splice sequence and may not result in an altered protein. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
MBD5-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
MBD5: BS1, BS2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at