rs376471354
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_003482.4(KMT2D):c.11670C>T(p.Ser3890=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,551,380 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 0.00030 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00038 ( 0 hom. )
Consequence
KMT2D
NM_003482.4 synonymous
NM_003482.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.38
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 12-49033035-G-A is Benign according to our data. Variant chr12-49033035-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 309027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.38 with no splicing effect.
BS2
?
High AC in GnomAd4 at 46 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.11670C>T | p.Ser3890= | synonymous_variant | 40/55 | ENST00000301067.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.11670C>T | p.Ser3890= | synonymous_variant | 40/55 | 5 | NM_003482.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000303 AC: 46AN: 151960Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000226 AC: 35AN: 154770Hom.: 0 AF XY: 0.000195 AC XY: 16AN XY: 81880
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GnomAD4 exome AF: 0.000380 AC: 532AN: 1399302Hom.: 0 Cov.: 48 AF XY: 0.000375 AC XY: 259AN XY: 690158
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GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152078Hom.: 0 Cov.: 33 AF XY: 0.000256 AC XY: 19AN XY: 74358
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | KMT2D: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 26, 2018 | - - |
Kabuki syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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