17-7885025-CCCGCCGCCGCCGCCG-CCCGCCG

Variant names:

• chr17-7885025-CCCGCCGCCG-C
• rs759738955
• NM_001437504.1:c.234_242delGCCGCCGCC

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS1

The NM_001437504.1(CHD3):​c.234_242delGCCGCCGCC​(p.Pro79_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 0.00045 in 1,161,190 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: CHD3 NM_001437504.1 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.422
• 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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001437504.1
• BP6: Variant 17-7885025-CCCGCCGCCG-C is Benign according to our data. Variant chr17-7885025-CCCGCCGCCG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2647420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00143 (205/143280) while in subpopulation AFR AF = 0.00362 (145/40054). AF 95% confidence interval is 0.00314. There are 0 homozygotes in GnomAd4. There are 92 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: 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.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.234_242delGCCGCCGCC	p.Pro79_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.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+131_-167+139delCGGCGGCGG		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 204 AN: 143180 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000621

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000615

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00699

Gnomad NFE AF: 0.000557

Gnomad OTH AF: 0.00203

GnomAD4 exome AF: 0.000312 AC: 318 AN: 1017910 Hom.: 1 AF XY: 0.000280 AC XY: 135 AN XY: 482964

African (AFR) AF: 0.00345 AC: 71 AN: 20582

American (AMR) AF: 0.000269 AC: 2 AN: 7446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11712

East Asian (EAS) AF: 0.000185 AC: 4 AN: 21582

South Asian (SAS) AF: 0.00126 AC: 25 AN: 19866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17760

Middle Eastern (MID) AF: 0.00345 AC: 9 AN: 2606

European-Non Finnish (NFE) AF: 0.000204 AC: 179 AN: 877526

Other (OTH) AF: 0.000721 AC: 28 AN: 38830

GnomAD4 genome AF: 0.00143 AC: 205 AN: 143280 Hom.: 0 Cov.: 27 AF XY: 0.00132 AC XY: 92 AN XY: 69602

African (AFR) AF: 0.00362 AC: 145 AN: 40054

American (AMR) AF: 0.000620 AC: 9 AN: 14512

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

East Asian (EAS) AF: 0.000616 AC: 3 AN: 4870

South Asian (SAS) AF: 0.00127 AC: 6 AN: 4712

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

Middle Eastern (MID) AF: 0.00752 AC: 2 AN: 266

European-Non Finnish (NFE) AF: 0.000557 AC: 36 AN: 64654

Other (OTH) AF: 0.00201 AC: 4 AN: 1990

Alfa AF: 0.0000549 Hom.: 4

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42
Mutation Taster		=169/31	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;