19-35720684-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_014727.3(KMT2B):c.1337C>T(p.Pro446Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,481,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P446P) has been classified as Benign.
Frequency
Consequence
NM_014727.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2B | NM_014727.3 | c.1337C>T | p.Pro446Leu | missense_variant | 3/37 | ENST00000420124.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2B | ENST00000420124.4 | c.1337C>T | p.Pro446Leu | missense_variant | 3/37 | 1 | NM_014727.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000667 AC: 1AN: 149956Hom.: 0 Cov.: 24
GnomAD3 exomes AF: 0.0000352 AC: 3AN: 85330Hom.: 0 AF XY: 0.0000466 AC XY: 2AN XY: 42918
GnomAD4 exome AF: 0.0000120 AC: 16AN: 1331192Hom.: 0 Cov.: 42 AF XY: 0.0000154 AC XY: 10AN XY: 650920
GnomAD4 genome AF: 0.00000667 AC: 1AN: 149956Hom.: 0 Cov.: 24 AF XY: 0.0000137 AC XY: 1AN XY: 73074
ClinVar
Submissions by phenotype
Dystonia 28, childhood-onset Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Mar 05, 2018 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at