17-7884893-CGAG-C

Variant names:

• chr17-7884893-CGAG-C
• rs770383628
• ENST00000700753.1:c.104_106delAGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001005271.3(CHD3):​c.104_106delAGG​(p.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 0.00619 in 1,232,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0069 (0 hom.)
• Consequence: CHD3 NM_001005271.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28

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 -10 ACMG points.

• BP6: Variant 17-7884893-CGAG-C is Benign according to our data. Variant chr17-7884893-CGAG-C is described in ClinVar as [Benign]. Clinvar id is 2647418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000322 (45/139660) while in subpopulation AFR AF= 0.000845 (32/37852). AF 95% confidence interval is 0.000615. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.104_106delAGG	p.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.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.104_106delAGG	p.Glu35del	disruptive_inframe_deletion	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+269_-167+271delCTC		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+269_74+271delCTC		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 45 AN: 139660 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000698

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.000674

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000633

Gnomad OTH AF: 0.000525

GnomAD3 exomes AF: 0.0131 AC: 774 AN: 59150 Hom.: 0 AF XY: 0.0134 AC XY: 433 AN XY: 32278

Gnomad AFR exome AF: 0.00830

Gnomad AMR exome AF: 0.0143

Gnomad ASJ exome AF: 0.0120

Gnomad EAS exome AF: 0.0113

Gnomad SAS exome AF: 0.0136

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.0123

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.00694 AC: 7590 AN: 1093256 Hom.: 0 AF XY: 0.00752 AC XY: 4050 AN XY: 538318

Gnomad4 AFR exome AF: 0.00684

Gnomad4 AMR exome AF: 0.0130

Gnomad4 ASJ exome AF: 0.00959

Gnomad4 EAS exome AF: 0.00747

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.00600

Gnomad4 OTH exome AF: 0.00747

GnomAD4 genome AF: 0.000322 AC: 45 AN: 139660 Hom.: 0 Cov.: 27 AF XY: 0.000324 AC XY: 22 AN XY: 67922

Gnomad4 AFR AF: 0.000845

Gnomad4 AMR AF: 0.0000698

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000226

Gnomad4 FIN AF: 0.000674

Gnomad4 NFE AF: 0.0000633

Gnomad4 OTH AF: 0.000525

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHD3: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;