ENST00000700753.1:c.121G>A

Variant names:

Variant summary

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

The ENST00000700753.1(CHD3):c.121G>A(p.Glu41Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,260,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 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. E41Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

CHD3
ENST00000700753.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Publications

0 publications found

Variant links:

Genes affected

CHD3 (HGNC:1918): (chromodomain helicase DNA binding protein 3) This gene encodes a member of the CHD family of proteins which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. This protein is one of the components of a histone deacetylase complex referred to as the Mi-2/NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Chromatin remodeling is essential for many processes including transcription. Autoantibodies against this protein are found in a subset of patients with dermatomyositis. Three alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CHD3 links:

NAA38 (HGNC:28212): (N-alpha-acetyltransferase 38, NatC auxiliary subunit) Involved in negative regulation of apoptotic process. Located in cytoplasm and nucleoplasm. Part of NatC complex. Colocalizes with polysome. [provided by Alliance of Genome Resources, Apr 2022]

NAA38 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=0.1534529).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000700753.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	NM_001437504.1	c.121G>A	p.Glu41Lys	missense	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
CHD3	NM_001005271.3	c.121G>A	p.Glu41Lys	missense	Exon 1 of 40	NP_001005271.2	Q12873-3
CHD3	NM_001437509.1	c.121G>A	p.Glu41Lys	missense	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	ENST00000700753.1		c.121G>A	p.Glu41Lys	missense	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9	TSL:2	c.121G>A	p.Glu41Lys	missense	Exon 1 of 40	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5	TSL:3	c.-167+238C>T		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000159

AC:

AN:

1260728

Hom.:

Cov.:

AF XY:

0.00000162

AC XY:

AN XY:

618084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26834

American (AMR)

AF:

0.00

AC:

AN:

26728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20308

East Asian (EAS)

AF:

0.00

AC:

AN:

28482

South Asian (SAS)

AF:

0.00

AC:

AN:

61238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3636

European-Non Finnish (NFE)

AF:

0.00000199

AC:

AN:

1005124

Other (OTH)

AF:

0.00

AC:

AN:

50774

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

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

Benign

0.18

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.95

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.59

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.48

PhyloP100

1.3

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.18

REVEL

Uncertain

0.29

Sift

Pathogenic

0.0

Sift4G

Benign

0.77

Vest4

0.082

MutPred

0.10

Gain of ubiquitination at E41 (P = 0.0114)

MVP

0.42

MPC

0.78

ClinPred

0.22

PromoterAI

0.050

Neutral

(source)

gMVP

0.076

Mutation Taster

=91/9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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