17-7885005-C-G

Variant names:

• chr17-7885005-C-G
• rs935201217
• NM_001437504.1:c.199C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001437504.1(CHD3):​c.199C>G​(p.Pro67Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,094,096 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P67S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CHD3 NM_001437504.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

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]

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]

ACMG classification

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=0.15202641).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD3	NM_001437504.1		c.199C>G	p.Pro67Ala	missense	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.199C>G	p.Pro67Ala	missense	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.199C>G	p.Pro67Ala	missense	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD3	ENST00000700753.1		c.199C>G	p.Pro67Ala	missense	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.199C>G	p.Pro67Ala	missense	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+160G>C		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1094096 Hom.: 0 Cov.: 30 AF XY: 0.00000384 AC XY: 2 AN XY: 521112

African (AFR) AF: 0.00 AC: 0 AN: 22750

American (AMR) AF: 0.00 AC: 0 AN: 9904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14608

East Asian (EAS) AF: 0.00 AC: 0 AN: 26436

South Asian (SAS) AF: 0.00 AC: 0 AN: 22638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2968

European-Non Finnish (NFE) AF: 0.00000216 AC: 2 AN: 925794

Other (OTH) AF: 0.00 AC: 0 AN: 43714

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.75
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.48	T
PhyloP100		2.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.21
Sift	Benign	0.043	D
Sift4G	Benign	0.47	T
Vest4		0.12
MutPred		0.15		Loss of catalytic residue at P67 (P = 0.1535)
MVP		0.36
MPC		0.68
ClinPred		0.076	T
GERP RS		-0.17
PromoterAI		0.098	Neutral
gMVP		0.070
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs935201217; hg19: chr17-7788323;