rs759738955

Variant names:

• chr17-7885025-CCCGCCGCCGCCGCCG-C
• rs759738955
• NM_001437504.1:c.228_242delGCCGCCGCCGCCGCC

Your query was ambiguous. Multiple possible variants found:

• chr17-7885025-CCCGCCGCCGCCGCCG-C
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG
• chr17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001437504.1(CHD3):​c.228_242delGCCGCCGCCGCCGCC​(p.Pro77_Pro81del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 1,017,932 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: CHD3 NM_001437504.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001437504.1

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.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
	CHD3	NM_001005271.3		c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3
	CHD3	NM_001437509.1		c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD3	ENST00000700753.1		c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
	CHD3	ENST00000380358.9	TSL:2	c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
	NAA38	ENST00000576861.5	TSL:3	c.-167+125_-167+139delCGGCGGCGGCGGCGG		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.000302 AC: 1 AN: 3314 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000855

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000619 AC: 63 AN: 1017932 Hom.: 0 AF XY: 0.0000621 AC XY: 30 AN XY: 482980

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20580

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: 0.00 AC: 0 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: 0.0000718 AC: 63 AN: 877538

Other (OTH) AF: 0.00 AC: 0 AN: 38834

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

Alfa AF: 0.00 Hom.: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

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;