chr9-137716972-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024757.5(EHMT1):​c.432C>T​(p.Ala144Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,611,144 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 13 hom. )

Consequence

EHMT1
NM_024757.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.787
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
Variant 9-137716972-C-T is Benign according to our data. Variant chr9-137716972-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 96162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.787 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00231 (352/152272) while in subpopulation NFE AF= 0.00376 (256/68014). AF 95% confidence interval is 0.00339. There are 2 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 352 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EHMT1NM_024757.5 linkuse as main transcriptc.432C>T p.Ala144Ala synonymous_variant 3/27 ENST00000460843.6 NP_079033.4 Q9H9B1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EHMT1ENST00000460843.6 linkuse as main transcriptc.432C>T p.Ala144Ala synonymous_variant 3/275 NM_024757.5 ENSP00000417980.1 Q9H9B1-1

Frequencies

GnomAD3 genomes
AF:
0.00231
AC:
352
AN:
152152
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00584
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00376
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00210
AC:
526
AN:
250344
Hom.:
1
AF XY:
0.00210
AC XY:
285
AN XY:
135552
show subpopulations
Gnomad AFR exome
AF:
0.000556
Gnomad AMR exome
AF:
0.000435
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00481
Gnomad NFE exome
AF:
0.00344
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00322
AC:
4694
AN:
1458872
Hom.:
13
Cov.:
31
AF XY:
0.00320
AC XY:
2324
AN XY:
725308
show subpopulations
Gnomad4 AFR exome
AF:
0.000479
Gnomad4 AMR exome
AF:
0.000560
Gnomad4 ASJ exome
AF:
0.0000766
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00687
Gnomad4 NFE exome
AF:
0.00374
Gnomad4 OTH exome
AF:
0.00219
GnomAD4 genome
AF:
0.00231
AC:
352
AN:
152272
Hom.:
2
Cov.:
32
AF XY:
0.00228
AC XY:
170
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00584
Gnomad4 NFE
AF:
0.00376
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00222
Hom.:
1
Bravo
AF:
0.00189

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Aug 19, 2013- -
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJun 01, 2015- -
not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2024EHMT1: BP4, BP7, BS2 -
Benign, criteria provided, single submitterclinical testingGeneDxAug 16, 2018- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 13, 2017This 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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
EHMT1-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 23, 2019This variant is classified as 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
-0.65
CADD
Benign
4.2
DANN
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs139461232; hg19: chr9-140611424; API