Genetic Variant CHD3:p.Asp59Val (chr17-7884982-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_001437504.1(CHD3):c.176A>T(p.Asp59Val) variant causes a missense 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. 14/20 in silico tools predict 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. D59G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 28)

Consequence

CHD3
NM_001437504.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0410

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=0.15354517).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001437504.1. 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.176A>T	p.Asp59Val	missense	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
CHD3	NM_001005271.3	c.176A>T	p.Asp59Val	missense	Exon 1 of 40	NP_001005271.2	Q12873-3
CHD3	NM_001437509.1	c.176A>T	p.Asp59Val	missense	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	ENST00000700753.1		c.176A>T	p.Asp59Val	missense	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9	TSL:2	c.176A>T	p.Asp59Val	missense	Exon 1 of 40	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5	TSL:3	c.-167+183T>A		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.69

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.50

PhyloP100

0.041

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.44

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Benign

0.31

Vest4

0.17

MutPred

0.27

Loss of solvent accessibility (P = 0.0052)

MVP

0.37

MPC

0.99

ClinPred

0.074

GERP RS

1.1

PromoterAI

0.089

Neutral

(source)

gMVP

0.13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over