17-7885025-CCCG-C

Variant names:

• chr17-7885025-CCCG-C
• rs759738955
• ENST00000700753.1:c.240_242delGCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001005271.3(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 NM_001005271.3 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.113

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 -16 ACMG points.

• BP6: Variant 17-7885025-CCCG-C is Benign according to our data. Variant chr17-7885025-CCCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 2343495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7885025-CCCG-C is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.240_242delGCC	p.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.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.240_242delGCC	p.Pro81del	disruptive_inframe_deletion	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+137_-167+139delCGG		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+137_74+139delCGG		intron_variant	Intron 1 of 4	5

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

GnomAD3 exomes AF: 0.00905 AC: 30 AN: 3314 Hom.: 0 AF XY: 0.0111 AC XY: 20 AN XY: 1804

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 SAS exome AF: 0.0207

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

Gnomad4 AFR exome AF: 0.00132

Gnomad4 AMR exome AF: 0.00589

Gnomad4 ASJ exome AF: 0.00155

Gnomad4 EAS exome AF: 0.00195

Gnomad4 SAS exome AF: 0.00256

Gnomad4 FIN exome AF: 0.00153

Gnomad4 NFE exome AF: 0.000772

Gnomad4 OTH exome AF: 0.000911

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

Gnomad4 AFR AF: 0.000624

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000928

Gnomad4 OTH AF: 0.00101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Jun 14, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

May 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHD3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs759738955; hg19: chr17-7788343;