17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCG

Variant names:

• chr17-7885025-C-CCCGCCGCCG
• rs759738955
• NM_001437504.1:c.234_242dupGCCGCCGCC

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_242dupGCCGCCGCC​(p.Pro79_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 0.000168 in 1,161,208 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: CHD3 NM_001437504.1 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001437504.1
• BP6: Variant 17-7885025-C-CCCGCCGCCG is Benign according to our data. Variant chr17-7885025-C-CCCGCCGCCG is described in ClinVar as Likely_benign. ClinVar VariationId is 4002102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000195 (28/143278) while in subpopulation AMR AF = 0.000551 (8/14512). AF 95% confidence interval is 0.000274. There are 0 homozygotes in GnomAd4. There are 11 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_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.234_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.234_242dupGCCGCCGCC	p.Pro79_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.234_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.234_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+131_-167+139dupCGGCGGCGG		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes AF: 0.000196 AC: 28 AN: 143178 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000552

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000201

Gnomad OTH AF: 0.00102

GnomAD4 exome AF: 0.000164 AC: 167 AN: 1017930 Hom.: 0 Cov.: 30 AF XY: 0.000155 AC XY: 75 AN XY: 482976

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

American (AMR) AF: 0.00 AC: 0 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: 0.000201 AC: 4 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: 0.000182 AC: 160 AN: 877534

Other (OTH) AF: 0.0000773 AC: 3 AN: 38834

GnomAD4 genome AF: 0.000195 AC: 28 AN: 143278 Hom.: 0 Cov.: 27 AF XY: 0.000158 AC XY: 11 AN XY: 69600

African (AFR) AF: 0.0000749 AC: 3 AN: 40054

American (AMR) AF: 0.000551 AC: 8 AN: 14512

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

East Asian (EAS) AF: 0.000205 AC: 1 AN: 4870

South Asian (SAS) AF: 0.000212 AC: 1 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: 0.000201 AC: 13 AN: 64652

Other (OTH) AF: 0.00101 AC: 2 AN: 1990

Alfa AF: 0.00 Hom.: 4

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.31
Mutation Taster		=84/16	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;