rs772711535

Variant names:

• chr17-7884848-G-A
• rs772711535
• ENST00000700753.1:c.42G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001005271.3(CHD3):​c.42G>A​(p.Glu14Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,115,704 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 25)
  • Exomes 𝑓: 0.00081 (4 hom.)
• Consequence: CHD3 NM_001005271.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.665

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]

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-7884848-G-A is Benign according to our data. Variant chr17-7884848-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 932351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.665 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000383 (57/148738) while in subpopulation SAS AF= 0.00492 (23/4674). AF 95% confidence interval is 0.00336. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD3	NM_001005271.3	c.42G>A	p.Glu14Glu	synonymous_variant	Exon 1 of 40		NP_001005271.2
CHD3	XM_005256427.5	c.42G>A	p.Glu14Glu	synonymous_variant	Exon 1 of 40		XP_005256484.1
CHD3	XM_006721423.4	c.42G>A	p.Glu14Glu	synonymous_variant	Exon 1 of 40		XP_006721486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD3	ENST00000700753.1	c.42G>A	p.Glu14Glu	synonymous_variant	Exon 1 of 40			ENSP00000515165.1
CHD3	ENST00000380358.9	c.42G>A	p.Glu14Glu	synonymous_variant	Exon 1 of 40	2		ENSP00000369716.4
NAA38	ENST00000576861.5	c.-167+317C>T		intron_variant	Intron 1 of 4	3		ENSP00000461545.1
NAA38	ENST00000570555.1	n.74+317C>T		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.000390 AC: 58 AN: 148634 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000492

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000332

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00513

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000407

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00197 AC: 157 AN: 79592 Hom.: 2 AF XY: 0.00253 AC XY: 113 AN XY: 44620

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000617

Gnomad ASJ exome AF: 0.000162

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00800

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000725

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000815 AC: 788 AN: 966966 Hom.: 4 Cov.: 13 AF XY: 0.000989 AC XY: 483 AN XY: 488584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000148

Gnomad4 ASJ exome AF: 0.0000511

Gnomad4 EAS exome AF: 0.0000377

Gnomad4 SAS exome AF: 0.00672

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000447

Gnomad4 OTH exome AF: 0.000895

GnomAD4 genome AF: 0.000383 AC: 57 AN: 148738 Hom.: 0 Cov.: 25 AF XY: 0.000524 AC XY: 38 AN XY: 72482

Gnomad4 AFR AF: 0.0000491

Gnomad4 AMR AF: 0.000331

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00492

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000407

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000437 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CHD3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs772711535; hg19: chr17-7788166;