rs201119371
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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.13644C>T(p.Ser4548=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,613,836 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0030 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0046 ( 26 hom. )
Consequence
KMT2D
NM_003482.4 synonymous
NM_003482.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0400
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=-0.55).
BP6
Variant 12-49030920-G-A is Benign according to our data. Variant chr12-49030920-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 94167.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49030920-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.04 with no splicing effect.
BS2
High AC in GnomAd4 at 461 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KMT2D | NM_003482.4 | c.13644C>T | p.Ser4548= | synonymous_variant | 41/55 | ENST00000301067.12 | NP_003473.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KMT2D | ENST00000301067.12 | c.13644C>T | p.Ser4548= | synonymous_variant | 41/55 | 5 | NM_003482.4 | ENSP00000301067 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00303 AC: 461AN: 152186Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00358 AC: 892AN: 248816Hom.: 4 AF XY: 0.00401 AC XY: 541AN XY: 135052
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GnomAD4 exome AF: 0.00455 AC: 6655AN: 1461532Hom.: 26 Cov.: 38 AF XY: 0.00473 AC XY: 3441AN XY: 727040
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GnomAD4 genome AF: 0.00303 AC: 461AN: 152304Hom.: 1 Cov.: 32 AF XY: 0.00291 AC XY: 217AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 21, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 18, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 26, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | KMT2D: BP4, BP7, BS1, BS2 - |
Kabuki syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 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
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