rs73578877
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_024757.5(EHMT1):c.3375-9A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,613,274 control chromosomes in the GnomAD database, including 10,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.15 ( 5310 hom., cov: 33)
Exomes 𝑓: 0.016 ( 4788 hom. )
Consequence
EHMT1
NM_024757.5 splice_polypyrimidine_tract, intron
NM_024757.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.000005028
2
Clinical Significance
Conservation
PhyloP100: 0.0360
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 9-137817430-A-C is Benign according to our data. Variant chr9-137817430-A-C is described in ClinVar as [Benign]. Clinvar id is 96155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EHMT1 | NM_024757.5 | c.3375-9A>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000460843.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EHMT1 | ENST00000460843.6 | c.3375-9A>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_024757.5 |
Frequencies
GnomAD3 genomes ? AF: 0.146 AC: 22099AN: 151380Hom.: 5291 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
22099
AN:
151380
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0393 AC: 9864AN: 250958Hom.: 2155 AF XY: 0.0290 AC XY: 3942AN XY: 135720
GnomAD3 exomes
AF:
AC:
9864
AN:
250958
Hom.:
AF XY:
AC XY:
3942
AN XY:
135720
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0162 AC: 23719AN: 1461776Hom.: 4788 Cov.: 31 AF XY: 0.0141 AC XY: 10257AN XY: 727194
GnomAD4 exome
AF:
AC:
23719
AN:
1461776
Hom.:
Cov.:
31
AF XY:
AC XY:
10257
AN XY:
727194
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.146 AC: 22161AN: 151498Hom.: 5310 Cov.: 33 AF XY: 0.141 AC XY: 10406AN XY: 74002
GnomAD4 genome
?
AF:
AC:
22161
AN:
151498
Hom.:
Cov.:
33
AF XY:
AC XY:
10406
AN XY:
74002
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
100
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 02, 2012 | - - |
Kleefstra syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 03, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
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