rs587778485
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_003482.4(KMT2D):c.14749C>T(p.Pro4917Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000259 in 1,543,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000022 ( 0 hom. )
Consequence
KMT2D
NM_003482.4 missense
NM_003482.4 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 5.53
Genes affected
KMT2D (HGNC:7133): (lysine methyltransferase 2D) The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KMT2D. . Gene score misZ 3.7288 (greater than the threshold 3.09). Trascript score misZ 4.6964 (greater than threshold 3.09). GenCC has associacion of gene with Kabuki syndrome, branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome, Kabuki syndrome 1, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.41247797).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.14749C>T | p.Pro4917Ser | missense_variant | 49/55 | ENST00000301067.12 | NP_003473.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.14749C>T | p.Pro4917Ser | missense_variant | 49/55 | 5 | NM_003482.4 | ENSP00000301067.7 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151836Hom.: 0 Cov.: 30
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GnomAD4 exome AF: 0.00000216 AC: 3AN: 1391282Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0AN XY: 685626
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GnomAD4 genome AF: 0.00000659 AC: 1AN: 151836Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74150
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ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
D
Polyphen
D
Vest4
MutPred
Gain of phosphorylation at P4917 (P = 6e-04);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at