ENST00000700753.1:c.225_242dupGCCGCCGCCGCCGCCGCC

Variant names:

• chr17-7885025-C-CCCGCCGCCGCCGCCGCCG
• ENST00000700753.1:c.225_242dupGCCGCCGCCGCCGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The ENST00000700753.1(CHD3):​c.225_242dupGCCGCCGCCGCCGCCGCC​(p.Pro76_Pro81dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 27)
  • Failed GnomAD Quality Control
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in ENST00000700753.1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.225_242dupGCCGCCGCCGCCGCCGCC	p.Pro76_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.225_242dupGCCGCCGCCGCCGCCGCC	p.Pro76_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.225_242dupGCCGCCGCCGCCGCCGCC	p.Pro76_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.225_242dupGCCGCCGCCGCCGCCGCC	p.Pro76_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.225_242dupGCCGCCGCCGCCGCCGCC	p.Pro76_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+122_-167+139dupCGGCGGCGGCGGCGGCGG		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+122_74+139dupCGGCGGCGGCGGCGGCGG		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 143180 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 143280 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 69602

Gnomad4 AFR AF: 0.00

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: 0.00

Gnomad4 OTH AF: 0.00

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7788343;