ENST00000700753.1:c.240_242dupGCC

Variant names:

• chr17-7885025-C-CCCG
• rs759738955
• ENST00000700753.1:c.240_242dupGCC

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The ENST00000700753.1(CHD3):​c.240_242dupGCC​(p.Pro81dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00874 in 1,161,150 control chromosomes in the GnomAD database, including 49 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (17 hom., cov: 27)
  • Exomes 𝑓: 0.0082 (32 hom.)
• Consequence: CHD3 ENST00000700753.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.312

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

Verdict is Benign. Variant got -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000700753.1
• BP6: Variant 17-7885025-C-CCCG is Benign according to our data. Variant chr17-7885025-C-CCCG is described in ClinVar as [Likely_benign]. Clinvar id is 1210084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1789/143262) while in subpopulation AFR AF= 0.0157 (628/40050). AF 95% confidence interval is 0.0147. There are 17 homozygotes in gnomad4. There are 837 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1789 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		XP_006721486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD3	ENST00000700753.1	c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+137_-167+139dupCGG		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+137_74+139dupCGG		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1784 AN: 143162 Hom.: 17 Cov.: 27

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.000410

Gnomad SAS AF: 0.00254

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0280

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00241 AC: 8 AN: 3314 Hom.: 0 AF XY: 0.00166 AC XY: 3 AN XY: 1804

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00968

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00230

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00893

GnomAD4 exome AF: 0.00821 AC: 8354 AN: 1017888 Hom.: 32 Cov.: 30 AF XY: 0.00813 AC XY: 3928 AN XY: 482952

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.00726

Gnomad4 EAS exome AF: 0.0000463

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.00253

Gnomad4 NFE exome AF: 0.00866

Gnomad4 OTH exome AF: 0.00708

GnomAD4 genome AF: 0.0125 AC: 1789 AN: 143262 Hom.: 17 Cov.: 27 AF XY: 0.0120 AC XY: 837 AN XY: 69586

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.0135

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.000411

Gnomad4 SAS AF: 0.00276

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.0151

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHD3: BS1, BS2 -

Dec 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs759738955; hg19: chr17-7788343;