ENST00000700753.1:c.234_242dupGCCGCCGCC

Variant names:

• chr17-7885025-C-CCCGCCGCCG
• rs759738955
• ENST00000700753.1:c.234_242dupGCCGCCGCC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The ENST00000700753.1(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: CHD3 ENST00000700753.1 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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 -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000700753.1
• 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 male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.234_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.234_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.234_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	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_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.234_242dupGCCGCCGCC	p.Pro79_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+131_-167+139dupCGGCGGCGG		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+131_74+139dupCGGCGGCGG		intron_variant	Intron 1 of 4	5

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000182

Gnomad4 OTH exome AF: 0.0000773

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

Gnomad4 AFR AF: 0.0000749

Gnomad4 AMR AF: 0.000551

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000205

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000201

Gnomad4 OTH AF: 0.00101

ClinVar

Not reported in ClinVar

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;