chr7-152162814-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PP2PP3BP4_StrongBP6_Very_StrongBS2
The NM_170606.3(KMT2C):c.10763C>T(p.Ser3588Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,614,094 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0028 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 13 hom. )
Consequence
KMT2C
NM_170606.3 missense
NM_170606.3 missense
Scores
8
6
3
Clinical Significance
Conservation
PhyloP100: 9.59
Genes affected
KMT2C (HGNC:13726): (lysine methyltransferase 2C) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a nuclear protein with an AT hook DNA-binding domain, a DHHC-type zinc finger, six PHD-type zinc fingers, a SET domain, a post-SET domain and a RING-type zinc finger. This protein is a member of the ASC-2/NCOA6 complex (ASCOM), which possesses histone methylation activity and is involved in transcriptional coactivation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KMT2C
PP3
?
Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, BayesDel_noAF, Eigen, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.014497042).
BP6
?
Variant 7-152162814-G-A is Benign according to our data. Variant chr7-152162814-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 134789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 428 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2C | NM_170606.3 | c.10763C>T | p.Ser3588Leu | missense_variant | 43/59 | ENST00000262189.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2C | ENST00000262189.11 | c.10763C>T | p.Ser3588Leu | missense_variant | 43/59 | 1 | NM_170606.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00281 AC: 428AN: 152110Hom.: 4 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00268 AC: 673AN: 250878Hom.: 5 AF XY: 0.00265 AC XY: 359AN XY: 135644
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GnomAD4 exome AF: 0.00315 AC: 4602AN: 1461866Hom.: 13 Cov.: 33 AF XY: 0.00316 AC XY: 2297AN XY: 727232
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33
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307
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | KMT2C: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
KMT2C-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 28, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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