chr17-7884935-T-A

Variant names:

• chr17-7884935-T-A
• rs1396427991
• NM_001437504.1:c.129T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001437504.1(CHD3):​c.129T>A​(p.Asp43Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000666 in 1,201,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D43Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: CHD3 NM_001437504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0880
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15303966).

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.129T>A	p.Asp43Glu	missense	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.129T>A	p.Asp43Glu	missense	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.129T>A	p.Asp43Glu	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.129T>A	p.Asp43Glu	missense	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.129T>A	p.Asp43Glu	missense	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+230A>T		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes AF: 0.00000682 AC: 1 AN: 146722 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 68054 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000666 AC: 8 AN: 1201796 Hom.: 0 Cov.: 32 AF XY: 0.0000119 AC XY: 7 AN XY: 588914

African (AFR) AF: 0.00 AC: 0 AN: 24766

American (AMR) AF: 0.00 AC: 0 AN: 24634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17764

East Asian (EAS) AF: 0.00 AC: 0 AN: 24498

South Asian (SAS) AF: 0.00 AC: 0 AN: 59294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3308

European-Non Finnish (NFE) AF: 0.00000824 AC: 8 AN: 970404

Other (OTH) AF: 0.00 AC: 0 AN: 46594

GnomAD4 genome Cov.: 28

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.71
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.36	T
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.60	T
PhyloP100		-0.088
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.010	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Benign	1.0	T
Vest4		0.14
MutPred		0.045		Loss of loop (P = 0.0374)
MVP		0.44
MPC		0.65
ClinPred		0.15	T
PromoterAI		0.049	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
gMVP		0.011

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: rs1396427991; hg19: chr17-7788253;