rs1354730657
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PVS1_ModeratePP3_StrongBP6_Moderate
The NM_024757.5(EHMT1):c.824-1G>T variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000096 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000063 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
EHMT1
NM_024757.5 splice_acceptor
NM_024757.5 splice_acceptor
Scores
4
2
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 2.39
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 Uncertain_significance. Variant got 4 ACMG points.
PVS1
?
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.0402874 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8, offset of 21, new splice context is: ttgcttgccttttgttttAGcag. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 9-137743370-G-T is Benign according to our data. Variant chr9-137743370-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 445623.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-137743370-G-T is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EHMT1 | NM_024757.5 | c.824-1G>T | splice_acceptor_variant | ENST00000460843.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EHMT1 | ENST00000460843.6 | c.824-1G>T | splice_acceptor_variant | 5 | NM_024757.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 13AN: 135320Hom.: 0 Cov.: 31 FAILED QC
GnomAD3 genomes
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000635 AC: 89AN: 1401980Hom.: 0 Cov.: 35 AF XY: 0.0000531 AC XY: 37AN XY: 696308
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000961 AC: 13AN: 135320Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 7AN XY: 65096
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?
Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 24, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D;D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at