12-49037164-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_003482.4(KMT2D):c.10192A>C(p.Met3398Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000628 in 1,592,044 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M3398V) has been classified as Likely benign.
Frequency
Consequence
NM_003482.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.10192A>C | p.Met3398Leu | missense_variant | 35/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.10192A>C | p.Met3398Leu | missense_variant | 35/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 240902Hom.: 0 AF XY: 0.00000766 AC XY: 1AN XY: 130610
GnomAD4 exome AF: 0.00000556 AC: 8AN: 1439808Hom.: 0 Cov.: 32 AF XY: 0.00000421 AC XY: 3AN XY: 712174
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74368
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 27, 2017 | - - |
Kabuki syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 09, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at