rs140693
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001276270.2(MBD4):c.1036G>A(p.Glu346Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,614,056 control chromosomes in the GnomAD database, including 4,120 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_001276270.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MBD4 | NM_001276270.2 | c.1036G>A | p.Glu346Lys | missense_variant | 3/8 | ENST00000429544.7 | NP_001263199.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MBD4 | ENST00000429544.7 | c.1036G>A | p.Glu346Lys | missense_variant | 3/8 | 1 | NM_001276270.2 | ENSP00000394080.2 |
Frequencies
GnomAD3 genomes AF: 0.0357 AC: 5423AN: 152114Hom.: 601 Cov.: 32
GnomAD3 exomes AF: 0.0583 AC: 14650AN: 251334Hom.: 2045 AF XY: 0.0508 AC XY: 6907AN XY: 135850
GnomAD4 exome AF: 0.0200 AC: 29184AN: 1461824Hom.: 3518 Cov.: 33 AF XY: 0.0193 AC XY: 14039AN XY: 727214
GnomAD4 genome AF: 0.0357 AC: 5437AN: 152232Hom.: 602 Cov.: 32 AF XY: 0.0410 AC XY: 3050AN XY: 74432
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | This variant is associated with the following publications: (PMID: 16803845, 19469655, 18495292, 23027038) - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 18, 2024 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at