Genetic Variant ENST00000700753.1:c.228_242delGCCGCCGCCGCCGCC (chr17-7885025-CCCGCCGCCGCCGCCG-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The ENST00000700753.1(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. 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
ENST00000700753.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Variant links:

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]

CHD3 links:

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]

NAA38 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000700753.1

BS2

High AC in GnomAdExome4 at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
CHD3	NM_001005271.3 link	c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3Q2TAZ1B3KWV4
CHD3	XM_005256427.5 link	c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	XP_005256484.1
CHD3	XM_006721423.4 link	c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	XP_006721486.1	A0A8V8TR54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CHD3	ENST00000700753.1 link	c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40		ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9 link	c.228_242delGCCGCCGCCGCCGCC	p.Pro77_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	2	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5 link	c.-167+125_-167+139delCGGCGGCGGCGGCGG		intron_variant	Intron 1 of 4	3	ENSP00000461545.1	I3L4V0
NAA38	ENST00000570555.1 link	n.74+125_74+139delCGGCGGCGGCGGCGG		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000302

AC:

AN:

3314

Hom.:

AF XY:

0.00

AC XY:

AN XY:

1804

show subpopulations

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 SAS 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:

AN:

1017932

Hom.:

AF XY:

0.0000621

AC XY:

AN XY:

482980

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000718

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over