Genetic Variant ENST00000700753.1:c.237_242delGCCGCC (chr17-7885025-CCCGCCG-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3BS1BS2

The ENST00000700753.1(CHD3):c.237_242delGCCGCC(p.Pro80_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 0.000104 in 1,161,154 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 0.00013 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

CHD3
ENST00000700753.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.113

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 Benign. Variant got -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000700753.1

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000133 (19/143280) while in subpopulation EAS AF= 0.00144 (7/4870). AF 95% confidence interval is 0.000675. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
CHD3	NM_001005271.3 link	c.237_242delGCCGCC	p.Pro80_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3Q2TAZ1B3KWV4
CHD3	XM_005256427.5 link	c.237_242delGCCGCC	p.Pro80_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	XP_005256484.1
CHD3	XM_006721423.4 link	c.237_242delGCCGCC	p.Pro80_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.237_242delGCCGCC	p.Pro80_Pro81del	disruptive_inframe_deletion	Exon 1 of 40		ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9 link	c.237_242delGCCGCC	p.Pro80_Pro81del	disruptive_inframe_deletion	Exon 1 of 40	2	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5 link	c.-167+134_-167+139delCGGCGG		intron_variant	Intron 1 of 4	3	ENSP00000461545.1	I3L4V0
NAA38	ENST00000570555.1 link	n.74+134_74+139delCGGCGG		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.000133

AC:

AN:

143180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00143

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000464

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000100

AC:

102

AN:

1017874

Hom.:

AF XY:

0.000106

AC XY:

AN XY:

482950

show subpopulations

Gnomad4 AFR exome

AF:

0.000583

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00111

Gnomad4 SAS exome

AF:

0.000201

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000593

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000133

AC:

AN:

143280

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

69602

show subpopulations

Gnomad4 AFR

AF:

0.000225

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00144

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000464

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