Genetic Variant EHMT1:p.Glu7Val (chr9-137619048-A-T) – 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.20A>T(p.Glu7Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EHMT1
NM_024757.5 missense, splice_region

Scores

Splicing: ADA: 0.7664

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.201

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 links:

ENSG00000283411 (HGNC:):

ENSG00000283411 links:

ARRDC1-AS1 (HGNC:23395): (ARRDC1 antisense RNA 1) This transcribed locus is thought to be non-coding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ARRDC1-AS1 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=0.19682407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024757.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
EHMT1	NM_024757.5	MANE Select	c.20A>T	p.Glu7Val	missense splice_region	Exon 1 of 27	NP_079033.4
EHMT1	NM_001354263.2		c.20A>T	p.Glu7Val	missense splice_region	Exon 1 of 27	NP_001341192.1
EHMT1	NM_001354259.2		c.-10A>T		splice_region	Exon 1 of 16	NP_001341188.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EHMT1	ENST00000460843.6	TSL:5 MANE Select	c.20A>T	p.Glu7Val	missense splice_region	Exon 1 of 27	ENSP00000417980.1	Q9H9B1-1
EHMT1	ENST00000462484.5	TSL:1	c.20A>T	p.Glu7Val	missense splice_region	Exon 1 of 16	ENSP00000417328.1	Q9H9B1-4
EHMT1	ENST00000896765.1		c.20A>T	p.Glu7Val	missense splice_region	Exon 1 of 28	ENSP00000566824.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

799906

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

369962

African (AFR)

AF:

0.00

AC:

AN:

15198

American (AMR)

AF:

0.00

AC:

AN:

1012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5004

East Asian (EAS)

AF:

0.00

AC:

AN:

3538

South Asian (SAS)

AF:

0.00

AC:

AN:

16540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1564

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

730462

Other (OTH)

AF:

0.00

AC:

AN:

26174

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.093

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.30

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.55

PhyloP100

0.20

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.59

REVEL

Benign

0.079

Sift

Uncertain

0.0070

Sift4G

Benign

0.071

Polyphen

0.016

Vest4

0.18

MutPred

0.26

Loss of solvent accessibility (P = 0.0062)

MVP

0.58

MPC

0.059

ClinPred

0.17

GERP RS

1.3

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.14

gMVP

0.13

Mutation Taster

=284/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.77

dbscSNV1_RF

Benign

0.65

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over