rs587778511
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4BP6_ModerateBS2
The NM_170606.3(KMT2C):c.12964C>T(p.Pro4322Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000231 in 1,599,754 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
KMT2C
NM_170606.3 missense
NM_170606.3 missense
Scores
1
9
7
Clinical Significance
Conservation
PhyloP100: 5.00
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 Likely_benign. Variant got -6 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, KMT2C
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3823107).
BP6
?
Variant 7-152148963-G-A is Benign according to our data. Variant chr7-152148963-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 134813.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2C | NM_170606.3 | c.12964C>T | p.Pro4322Ser | missense_variant | 52/59 | ENST00000262189.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2C | ENST00000262189.11 | c.12964C>T | p.Pro4322Ser | missense_variant | 52/59 | 1 | NM_170606.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152128Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000549 AC: 13AN: 236722Hom.: 0 AF XY: 0.0000551 AC XY: 7AN XY: 127110
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GnomAD4 exome AF: 0.0000228 AC: 33AN: 1447626Hom.: 0 Cov.: 32 AF XY: 0.0000250 AC XY: 18AN XY: 718612
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74312
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 15, 2022 | - - |
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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
T
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