12-49033555-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_003482.4(KMT2D):āc.11150A>Cā(p.Gln3717Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Q3717R) has been classified as Benign.
Frequency
Consequence
NM_003482.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.11150A>C | p.Gln3717Pro | missense_variant | 40/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.11150A>C | p.Gln3717Pro | missense_variant | 40/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000805 AC: 2AN: 248342Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134940
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461344Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0AN XY: 726962
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152072Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
Kabuki syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 20, 2012 | - - |
KMT2D-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 09, 2024 | The KMT2D c.11150A>C variant is predicted to result in the amino acid substitution p.Gln3717Pro. This variant was reported as uncertain significance in an individual with unspecified phenotypes from a study investigating Kabuki syndrome-specific epigenome signature. However, this variant was not considered to share the epigenome signature as seen in other pathogenic loss-of-function KMT2D variants (Sample KMT2D-24 in Table S5, Butcher et al. 2017. PubMed ID: 28475860). This variant is present in two out of ~248,000 alleles in gnomAD. 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at