rs587778457
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_003482.4(KMT2D):c.5129C>T(p.Thr1710Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,612,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_003482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.5129C>T | p.Thr1710Met | missense_variant | 22/55 | ENST00000301067.12 | NP_003473.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.5129C>T | p.Thr1710Met | missense_variant | 22/55 | 5 | NM_003482.4 | ENSP00000301067.7 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 152038Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000442 AC: 11AN: 249090Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135154
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460828Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 726670
GnomAD4 genome AF: 0.000132 AC: 20AN: 152038Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7AN XY: 74242
ClinVar
Submissions by phenotype
KMT2D-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 11, 2023 | The KMT2D c.5129C>T variant is predicted to result in the amino acid substitution p.Thr1710Met. This variant was reported in an individual with heterotaxy syndrome (Liang et al. 2020. PubMed ID: 32738303). This variant is reported in 0.046% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-49438042-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Kabuki syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 10, 2023 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at