Genetic Variant CHD3:p.Glu34_Glu35del (chr17-7884893-CGAGGAG-C) – 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.101_106delAGGAGG(p.Glu34_Glu35del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000492 in 1,280,306 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 0.000036 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CHD3
NM_001437504.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.00

Publications

2 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.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
CHD3	NM_001005271.3	c.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40	NP_001005271.2	Q12873-3
CHD3	NM_001437509.1	c.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	ENST00000700753.1		c.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9	TSL:2	c.101_106delAGGAGG	p.Glu34_Glu35del	disruptive_inframe_deletion	Exon 1 of 40	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5	TSL:3	c.-167+266_-167+271delCTCCTC		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

139746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000698

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000215

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000158

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000118

AC:

AN:

59150

AF XY:

0.000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000277

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000376

Gnomad FIN exome

AF:

0.000151

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000509

AC:

AN:

1140472

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

563012

show subpopulations

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

African (AFR)

AF:

0.0000865

AC:

AN:

23128

American (AMR)

AF:

0.000265

AC:

AN:

22678

Ashkenazi Jewish (ASJ)

AF:

0.000114

AC:

AN:

17486

East Asian (EAS)

AF:

0.0000418

AC:

AN:

23910

South Asian (SAS)

AF:

0.000121

AC:

AN:

58060

European-Finnish (FIN)

AF:

0.0000916

AC:

AN:

32764

Middle Eastern (MID)

AF:

0.000308

AC:

AN:

3244

European-Non Finnish (NFE)

AF:

0.0000372

AC:

AN:

914734

Other (OTH)

AF:

0.0000450

AC:

AN:

44468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000123441), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.372

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

AF:

0.0000358

AC:

AN:

139834

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

68050

show subpopulations

African (AFR)

AF:

0.0000527

AC:

AN:

37970

American (AMR)

AF:

0.0000697

AC:

AN:

14348

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3278

East Asian (EAS)

AF:

0.000215

AC:

AN:

4644

South Asian (SAS)

AF:

0.00

AC:

AN:

4412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0000158

AC:

AN:

63230

Other (OTH)

AF:

0.00

AC:

AN:

1924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.0

Mutation Taster

=183/17

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over