Genetic Variant CHD3:p.Pro77_Pro81dup (chr17-7885025-C-CCCGCCGCCGCCGCCG) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

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

The NM_001437504.1(CHD3):c.228_242dupGCCGCCGCCGCCGCC(p.Pro77_Pro81dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_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: 0.0000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHD3
NM_001437504.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

Publications

0 publications found

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 was made for transcript

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

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	NM_001437504.1	c.228_242dupGCCGCCGCCGCCGCC	p.Pro77_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
CHD3	NM_001005271.3	c.228_242dupGCCGCCGCCGCCGCC	p.Pro77_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001005271.2	Q12873-3
CHD3	NM_001437509.1	c.228_242dupGCCGCCGCCGCCGCC	p.Pro77_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	ENST00000700753.1		c.228_242dupGCCGCCGCCGCCGCC	p.Pro77_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9	TSL:2	c.228_242dupGCCGCCGCCGCCGCC	p.Pro77_Pro81dup	disruptive_inframe_insertion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5	TSL:3	c.-167+125_-167+139dupCGGCGGCGGCGGCGG		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000295

AC:

AN:

1017936

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

482982

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

20582

American (AMR)

AF:

0.00

AC:

AN:

7448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11712

East Asian (EAS)

AF:

0.00

AC:

AN:

21584

South Asian (SAS)

AF:

0.00

AC:

AN:

19870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17760

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2606

European-Non Finnish (NFE)

AF:

0.00000342

AC:

AN:

877540

Other (OTH)

AF:

0.00

AC:

AN:

38834

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00400497), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.31

Splicing

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

Publications

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17-7885025-CCCGCCGCCGCCGCCG-CCCGCCGCCGCCGCCGCCGCCGCCGCCGCCG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over