Genetic Variant CHD3:p.Pro80_Pro81dup (chr17-7885025-C-CCCGCCG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001005271.3(CHD3):c.237_242dupGCCGCC(p.Pro80_Pro81dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000594 in 1,161,206 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 0.000063 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

CHD3
NM_001005271.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

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 -4 ACMG points.

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
CHD3	NM_001005271.3 link	c.237_242dupGCCGCC	p.Pro80_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001005271.2	Q12873-3Q2TAZ1B3KWV4
CHD3	XM_005256427.5 link	c.237_242dupGCCGCC	p.Pro80_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	XP_005256484.1
CHD3	XM_006721423.4 link	c.237_242dupGCCGCC	p.Pro80_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	XP_006721486.1	A0A8V8TR54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CHD3	ENST00000700753.1 link	c.237_242dupGCCGCC	p.Pro80_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40		ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9 link	c.237_242dupGCCGCC	p.Pro80_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	2	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5 link	c.-167+134_-167+139dupCGGCGG		intron_variant	Intron 1 of 4	3	ENSP00000461545.1	I3L4V0
NAA38	ENST00000570555.1 link	n.74+134_74+139dupCGGCGG		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.0000629

AC:

AN:

143178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000501

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000138

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:

0.0000773

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000589

AC:

AN:

1017930

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

482982

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.0000627

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.0000628

AC:

AN:

143276

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69600

show subpopulations

Gnomad4 AFR

AF:

0.0000499

Gnomad4 AMR

AF:

0.000138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000773

Gnomad4 OTH

AF:

0.00

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