chr9-137619048-A-G

Variant names:

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>G(p.Glu7Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 799,906 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. 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. E7K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

EHMT1
NM_024757.5 missense, splice_region

Scores

Splicing: ADA: 0.9366

Clinical Significance

Not reported in ClinVar

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=0.19558343).

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>G	p.Glu7Gly	missense splice_region	Exon 1 of 27	NP_079033.4
EHMT1	NM_001354263.2		c.20A>G	p.Glu7Gly	missense splice_region	Exon 1 of 27	NP_001341192.1
EHMT1	NM_001354259.2		c.-10A>G		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>G	p.Glu7Gly	missense splice_region	Exon 1 of 27	ENSP00000417980.1	Q9H9B1-1
EHMT1	ENST00000462484.5	TSL:1	c.20A>G	p.Glu7Gly	missense splice_region	Exon 1 of 16	ENSP00000417328.1	Q9H9B1-4
EHMT1	ENST00000896765.1		c.20A>G	p.Glu7Gly	missense splice_region	Exon 1 of 28	ENSP00000566824.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000125

AC:

AN:

799906

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

369962

show subpopulations

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:

0.00000137

AC:

AN:

730462

Other (OTH)

AF:

0.00

AC:

AN:

26174

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.29

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.55

PhyloP100

0.20

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.80

REVEL

Benign

0.086

Sift

Uncertain

0.010

Sift4G

Benign

0.10

Polyphen

0.016

Vest4

0.089

MutPred

0.18

Gain of loop (P = 0.0045)

MVP

0.49

MPC

0.055

ClinPred

0.16

GERP RS

1.3

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.10

gMVP

0.069

Mutation Taster

=278/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.94

dbscSNV1_RF

Benign

0.67

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over