ENST00000700753.1:c.164G>C

Variant names:

• chr17-7884970-G-C
• NM_001437504.1:c.164G>C

Variant summary

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

The ENST00000700753.1(CHD3):​c.164G>C​(p.Gly55Ala) 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. 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. G55R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHD3 ENST00000700753.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.661
• 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=0.18920776).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD3	NM_001437504.1		c.164G>C	p.Gly55Ala	missense	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.164G>C	p.Gly55Ala	missense	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.164G>C	p.Gly55Ala	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.164G>C	p.Gly55Ala	missense	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.164G>C	p.Gly55Ala	missense	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+195C>G		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.51e-7 AC: 1 AN: 1175404 Hom.: 0 Cov.: 32 AF XY: 0.00000176 AC XY: 1 AN XY: 569092

African (AFR) AF: 0.00 AC: 0 AN: 24760

American (AMR) AF: 0.00 AC: 0 AN: 18370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17056

East Asian (EAS) AF: 0.00 AC: 0 AN: 27180

South Asian (SAS) AF: 0.00 AC: 0 AN: 44414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3238

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 961778

Other (OTH) AF: 0.00 AC: 0 AN: 46900

GnomAD4 genome Cov.: 28

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.64
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.43	T
PhyloP100		0.66
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
Vest4		0.12
MutPred		0.34		Loss of methylation at R54 (P = 0.0584)
MVP		0.45
MPC		0.75
ClinPred		0.14	T
GERP RS		1.1
PromoterAI		-0.090	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.049

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

hg19: chr17-7788288;