rs566701810

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024757.5(EHMT1):​c.85+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,585,322 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 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

EHMT1
NM_024757.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.245
Variant links:
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=-1.0).
BP6
Variant 9-137711039-G-A is Benign according to our data. Variant chr9-137711039-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000151 (23/152280) while in subpopulation AMR AF= 0.000981 (15/15298). AF 95% confidence interval is 0.000604. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EHMT1NM_024757.5 linkuse as main transcriptc.85+9G>A intron_variant ENST00000460843.6 NP_079033.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EHMT1ENST00000460843.6 linkuse as main transcriptc.85+9G>A intron_variant 5 NM_024757.5 ENSP00000417980 Q9H9B1-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000982
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000556
AC:
11
AN:
197832
Hom.:
0
AF XY:
0.0000187
AC XY:
2
AN XY:
106952
show subpopulations
Gnomad AFR exome
AF:
0.0000895
Gnomad AMR exome
AF:
0.0000346
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000239
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000230
Gnomad OTH exome
AF:
0.000197
GnomAD4 exome
AF:
0.0000272
AC:
39
AN:
1433042
Hom.:
0
Cov.:
31
AF XY:
0.0000211
AC XY:
15
AN XY:
709902
show subpopulations
Gnomad4 AFR exome
AF:
0.0000606
Gnomad4 AMR exome
AF:
0.0000495
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000520
Gnomad4 SAS exome
AF:
0.000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000173
Gnomad4 OTH exome
AF:
0.0000337
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152280
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.000981
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000130
Hom.:
0
Bravo
AF:
0.000159

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Kleefstra syndrome 1 Benign:2
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 26, 2024- -
Likely benign, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaMar 01, 2019This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: BP4,BP6. -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 22, 2016- -
EHMT1-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesNov 21, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
3.6
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs566701810; hg19: chr9-140605491; API