ENST00000700753.1:c.240_242delGCC

Variant names:

• chr17-7885025-CCCG-C
• rs759738955
• NM_001437504.1:c.240_242delGCC

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS1

The ENST00000700753.1(CHD3):​c.240_242delGCC​(p.Pro81del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000825 in 1,150,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00091 (0 hom.)
• Consequence: CHD3 ENST00000700753.1 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.113
• 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: Benign. The variant received -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000700753.1
• BP6: Variant 17-7885025-CCCG-C is Benign according to our data. Variant chr17-7885025-CCCG-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2343495.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 = 0.00023 (33/143272) while in subpopulation AFR AF = 0.000624 (25/40052). AF 95% confidence interval is 0.000433. There are 0 homozygotes in GnomAd4. There are 15 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

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.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD3	ENST00000700753.1		c.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+137_-167+139delCGG		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 33 AN: 143174 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000626

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000928

Gnomad OTH AF: 0.00102

GnomAD2 exomes AF: 0.00905 AC: 30 AN: 3314 AF XY: 0.0111

Gnomad AFR exome AF: 0.0156

Gnomad AMR exome AF: 0.00847

Gnomad ASJ exome AF: 0.0226

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00427

Gnomad OTH exome AF: 0.00893

GnomAD4 exome AF: 0.000910 AC: 916 AN: 1006884 Hom.: 0 AF XY: 0.000986 AC XY: 471 AN XY: 477532

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00132 AC: 27 AN: 20464

American (AMR) AF: 0.00589 AC: 43 AN: 7304

Ashkenazi Jewish (ASJ) AF: 0.00155 AC: 18 AN: 11604

East Asian (EAS) AF: 0.00195 AC: 42 AN: 21500

South Asian (SAS) AF: 0.00256 AC: 50 AN: 19548

European-Finnish (FIN) AF: 0.00153 AC: 27 AN: 17692

Middle Eastern (MID) AF: 0.00154 AC: 4 AN: 2590

European-Non Finnish (NFE) AF: 0.000772 AC: 670 AN: 867746

Other (OTH) AF: 0.000911 AC: 35 AN: 38436

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000230 AC: 33 AN: 143272 Hom.: 0 Cov.: 27 AF XY: 0.000216 AC XY: 15 AN XY: 69596

African (AFR) AF: 0.000624 AC: 25 AN: 40052

American (AMR) AF: 0.00 AC: 0 AN: 14508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3374

East Asian (EAS) AF: 0.00 AC: 0 AN: 4870

South Asian (SAS) AF: 0.00 AC: 0 AN: 4712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000928 AC: 6 AN: 64652

Other (OTH) AF: 0.00101 AC: 2 AN: 1990

Alfa AF: 0.00 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11
Mutation Taster		=84/16	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: rs759738955; hg19: chr17-7788343;