Genetic Variant EHMT1:p.Gly157Ala (chr9-137717010-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024757.5(EHMT1):c.470G>C(p.Gly157Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G157V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EHMT1
NM_024757.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.65

Publications

0 publications found

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]

EHMT1 Gene-Disease associations (from GenCC):

Kleefstra syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Kleefstra syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

EHMT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23940006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EHMT1	NM_024757.5 link	c.470G>C	p.Gly157Ala	missense_variant	Exon 3 of 27	ENST00000460843.6	NP_079033.4	Q9H9B1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EHMT1	ENST00000460843.6 link	c.470G>C	p.Gly157Ala	missense_variant	Exon 3 of 27	5	NM_024757.5	ENSP00000417980.1		Q9H9B1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33248

American (AMR)

AF:

0.00

AC:

AN:

44390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25982

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39586

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107720

Other (OTH)

AF:

0.00

AC:

AN:

60076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

T;.;T;T;T;T;.;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.86

D;D;T;T;D;T;T;D;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.24

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

1.8

L;L;.;.;.;.;.;.;.

PhyloP100

4.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.52

N;N;.;.;.;.;.;.;.

REVEL

Benign

0.14

Sift

Benign

0.11

T;T;.;.;.;.;.;.;.

Sift4G

Benign

0.37

T;T;T;.;.;T;D;.;T

Polyphen

0.99

D;P;.;.;.;.;.;.;.

Vest4

0.46

MutPred

0.097

Gain of glycosylation at T154 (P = 0.0794);Gain of glycosylation at T154 (P = 0.0794);.;Gain of glycosylation at T154 (P = 0.0794);.;.;.;.;.;

MVP

0.61

MPC

0.14

ClinPred

0.60

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.072

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over