17-7885025-CCCGCCGCCGCCGCCG-CCCGCCG

Variant names:

• chr17-7885025-CCCGCCGCCG-C
• rs759738955
• ENST00000700753.1:c.234_242delGCCGCCGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001005271.3(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_001005271.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.422

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 -10 ACMG points.

• 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 id 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 male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 205 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40		XP_006721486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD3	ENST00000700753.1	c.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.234_242delGCCGCCGCC	p.Pro79_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+131_-167+139delCGGCGGCGG		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+131_74+139delCGGCGGCGG		intron_variant	Intron 1 of 4	5

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

Gnomad4 AFR exome AF: 0.00345

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000185

Gnomad4 SAS exome AF: 0.00126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000204

Gnomad4 OTH exome AF: 0.000721

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

Gnomad4 AFR AF: 0.00362

Gnomad4 AMR AF: 0.000620

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000616

Gnomad4 SAS AF: 0.00127

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000557

Gnomad4 OTH AF: 0.00201

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHD3: PM4, BS1 -

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;