17-7885025-CCCGCCGCCGCCGCCG-CCCG

Variant names:

• chr17-7885025-CCCGCCGCCGCCG-C
• rs759738955
• NM_001437504.1:c.231_242delGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS1

The NM_001437504.1(CHD3):​c.231_242delGCCGCCGCCGCC​(p.Pro78_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 0.0000603 in 1,161,208 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000049 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: CHD3 NM_001437504.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001437504.1
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000619 (63/1017928) while in subpopulation AMR AF = 0.000403 (3/7448). AF 95% confidence interval is 0.000109. There are 0 homozygotes in GnomAdExome4. There are 30 alleles in the male GnomAdExome4 subpopulation. 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.231_242delGCCGCCGCCGCC	p.Pro78_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.231_242delGCCGCCGCCGCC	p.Pro78_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.231_242delGCCGCCGCCGCC	p.Pro78_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.231_242delGCCGCCGCCGCC	p.Pro78_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.231_242delGCCGCCGCCGCC	p.Pro78_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+128_-167+139delCGGCGGCGGCGG		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes AF: 0.0000489 AC: 7 AN: 143180 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000690

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: 0.00

GnomAD4 exome AF: 0.0000619 AC: 63 AN: 1017928 Hom.: 0 AF XY: 0.0000621 AC XY: 30 AN XY: 482980

African (AFR) AF: 0.00 AC: 0 AN: 20582

American (AMR) AF: 0.000403 AC: 3 AN: 7448

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 21584

South Asian (SAS) AF: 0.00 AC: 0 AN: 19870

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2606

European-Non Finnish (NFE) AF: 0.0000627 AC: 55 AN: 877532

Other (OTH) AF: 0.000129 AC: 5 AN: 38834

GnomAD4 genome AF: 0.0000489 AC: 7 AN: 143280 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 69600

African (AFR) AF: 0.00 AC: 0 AN: 40056

American (AMR) AF: 0.0000689 AC: 1 AN: 14512

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4868

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: 64654

Other (OTH) AF: 0.00 AC: 0 AN: 1990

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=176/24	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;