17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCG

Variant names:

• chr17-7885025-C-CCCG
• rs759738955
• NM_001437504.1:c.240_242dupGCC

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001437504.1(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 NM_001437504.1 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.312
• 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001437504.1
• BP6: Variant 17-7885025-C-CCCG is Benign according to our data. Variant chr17-7885025-C-CCCG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

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.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	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_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.240_242dupGCC	p.Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+137_-167+139dupCGG		intron	N/A	ENSP00000461545.1	I3L4V0

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

GnomAD2 exomes AF: 0.00241 AC: 8 AN: 3314 AF XY: 0.00166

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 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

African (AFR) AF: 0.0123 AC: 254 AN: 20582

American (AMR) AF: 0.00309 AC: 23 AN: 7448

Ashkenazi Jewish (ASJ) AF: 0.00726 AC: 85 AN: 11712

East Asian (EAS) AF: 0.0000463 AC: 1 AN: 21584

South Asian (SAS) AF: 0.00171 AC: 34 AN: 19868

European-Finnish (FIN) AF: 0.00253 AC: 45 AN: 17758

Middle Eastern (MID) AF: 0.0138 AC: 36 AN: 2606

European-Non Finnish (NFE) AF: 0.00866 AC: 7601 AN: 877502

Other (OTH) AF: 0.00708 AC: 275 AN: 38828

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

African (AFR) AF: 0.0157 AC: 628 AN: 40050

American (AMR) AF: 0.0135 AC: 196 AN: 14510

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 63 AN: 3374

East Asian (EAS) AF: 0.000411 AC: 2 AN: 4870

South Asian (SAS) AF: 0.00276 AC: 13 AN: 4712

European-Finnish (FIN) AF: 0.0182 AC: 145 AN: 7964

Middle Eastern (MID) AF: 0.0338 AC: 9 AN: 266

European-Non Finnish (NFE) AF: 0.0109 AC: 703 AN: 64648

Other (OTH) AF: 0.0151 AC: 30 AN: 1990

Alfa AF: 0.00577 Hom.: 4

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.31
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs759738955; hg19: chr17-7788343; COSMIC: COSV57872795; COSMIC: COSV57872795;