chr17-7893853-G-T

Variant names:

• chr17-7893853-G-T
• rs139173826
• NM_001005273.3:c.842G>T

Variant summary

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

The NM_001005273.3(CHD3):​c.842G>T​(p.Arg281Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R281C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CHD3 NM_001005273.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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]

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=0.23388568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005273.3	c.842G>T	p.Arg281Leu	missense_variant	Exon 6 of 40	ENST00000330494.12	NP_001005273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD3	ENST00000330494.12	c.842G>T	p.Arg281Leu	missense_variant	Exon 6 of 40	1	NM_001005273.3	ENSP00000332628.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251478 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461832 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727214

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	0.97
DEOGEN2	Benign	0.041	.;.;T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Uncertain	-0.085	T
MutationAssessor	Benign	0.90	.;L;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.26
Sift	Benign	0.049	D;D;D
Sift4G	Uncertain	0.057	T;D;D
Polyphen		0.15, 0.15	.;B;B
Vest4		0.37
MutPred		0.21		.;Loss of methylation at R281 (P = 0.0152);Loss of methylation at R281 (P = 0.0152);
MVP		0.78
MPC		1.1
ClinPred		0.83	D
GERP RS		5.3
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.097
gMVP		0.54
Mutation Taster		=90/10	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

Publications

LitVar

Other links and lift over

dbSNP: rs139173826; hg19: chr17-7797171;