17-7884893-CGAGGAGGAG-CGAG

Variant names:

• chr17-7884893-CGAGGAG-C
• rs770383628
• ENST00000700753.1:c.101_106delAGGAGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001005271.3(CHD3):​c.101_106delAGGAGG​(p.Glu34_Glu35del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,280,306 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 0.000036 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: CHD3 NM_001005271.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000509 (58/1140472) while in subpopulation MID AF= 0.000308 (1/3244). AF 95% confidence interval is 0.000115. There are 0 homozygotes in gnomad4_exome. There are 29 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.101_106delAGGAGG	p.Glu34_Glu35del	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.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+266_-167+271delCTCCTC		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+266_74+271delCTCCTC		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0000358 AC: 5 AN: 139746 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000698

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000215

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000158

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000118 AC: 7 AN: 59150 Hom.: 0 AF XY: 0.000155 AC XY: 5 AN XY: 32278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000277

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000376

Gnomad SAS exome AF: 0.000185

Gnomad FIN exome AF: 0.000151

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000509 AC: 58 AN: 1140472 Hom.: 0 AF XY: 0.0000515 AC XY: 29 AN XY: 563012

Gnomad4 AFR exome AF: 0.0000865

Gnomad4 AMR exome AF: 0.000265

Gnomad4 ASJ exome AF: 0.000114

Gnomad4 EAS exome AF: 0.0000418

Gnomad4 SAS exome AF: 0.000121

Gnomad4 FIN exome AF: 0.0000916

Gnomad4 NFE exome AF: 0.0000372

Gnomad4 OTH exome AF: 0.0000450

GnomAD4 genome AF: 0.0000358 AC: 5 AN: 139834 Hom.: 0 Cov.: 27 AF XY: 0.0000441 AC XY: 3 AN XY: 68050

Gnomad4 AFR AF: 0.0000527

Gnomad4 AMR AF: 0.0000697

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000215

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000158

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

LitVar

Other links and lift over

dbSNP: rs770383628; hg19: chr17-7788211;