rs765407306
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong
The NM_024757.5(EHMT1):c.3035+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000311 in 1,608,306 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
EHMT1
NM_024757.5 splice_donor_region, intron
NM_024757.5 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00008847
2
Clinical Significance
Conservation
PhyloP100: 2.36
Genes affected
EHMT1 (HGNC:24650): (euchromatic histone lysine methyltransferase 1) The protein encoded by this gene is a histone methyltransferase that methylates the lysine-9 position of histone H3. This action marks the genomic region packaged with these methylated histones for transcriptional repression. This protein may be involved in the silencing of MYC- and E2F-responsive genes and therefore could play a role in the G0/G1 cell cycle transition. Defects in this gene are a cause of chromosome 9q subtelomeric deletion syndrome (9q-syndrome, also known as Kleefstra syndrome). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 9-137813176-G-A is Benign according to our data. Variant chr9-137813176-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 366023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EHMT1 | NM_024757.5 | c.3035+3G>A | splice_donor_region_variant, intron_variant | ENST00000460843.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EHMT1 | ENST00000460843.6 | c.3035+3G>A | splice_donor_region_variant, intron_variant | 5 | NM_024757.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245576Hom.: 0 AF XY: 0.00000749 AC XY: 1AN XY: 133530
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GnomAD4 exome AF: 0.0000330 AC: 48AN: 1456156Hom.: 0 Cov.: 32 AF XY: 0.0000359 AC XY: 26AN XY: 724696
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74316
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 24, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Kleefstra syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at