ENST00000700753.1:c.121G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_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. 11/17 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the CHD3 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 48 curated pathogenic missense variants (we use a threshold of 10). The gene has 39 curated benign missense variants. Gene score misZ: 6.1518 (above the threshold of 3.09). GenCC associations: The gene is linked to Snijders Blok-Campeau syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.1534529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
CHD3	NM_001005271.3 link	c.121G>A	p.Glu41Lys	missense_variant	Exon 1 of 40	NP_001005271.2	Q12873-3Q2TAZ1B3KWV4
CHD3	XM_005256427.5 link	c.121G>A	p.Glu41Lys	missense_variant	Exon 1 of 40	XP_005256484.1
CHD3	XM_006721423.4 link	c.121G>A	p.Glu41Lys	missense_variant	Exon 1 of 40	XP_006721486.1	A0A8V8TR54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CHD3	ENST00000700753.1 link	c.121G>A	p.Glu41Lys	missense_variant	Exon 1 of 40		ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9 link	c.121G>A	p.Glu41Lys	missense_variant	Exon 1 of 40	2	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5 link	c.-167+238C>T		intron_variant	Intron 1 of 4	3	ENSP00000461545.1	I3L4V0
NAA38	ENST00000570555.1 link	n.74+238C>T		intron_variant	Intron 1 of 4	5

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000199

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

May 23, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

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

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

gMVP

0.076

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over