rs935201217

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001437504.1(CHD3):c.199C>A(p.Pro67Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000403 in 1,240,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P67S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

CHD3
NM_001437504.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15968233).

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.199C>A	p.Pro67Thr	missense	Exon 1 of 40	NP_001424433.1	A0A8V8TR54
CHD3	NM_001005271.3	c.199C>A	p.Pro67Thr	missense	Exon 1 of 40	NP_001005271.2	Q12873-3
CHD3	NM_001437509.1	c.199C>A	p.Pro67Thr	missense	Exon 1 of 40	NP_001424438.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD3	ENST00000700753.1		c.199C>A	p.Pro67Thr	missense	Exon 1 of 40	ENSP00000515165.1	A0A8V8TR54
CHD3	ENST00000380358.9	TSL:2	c.199C>A	p.Pro67Thr	missense	Exon 1 of 40	ENSP00000369716.4	Q12873-3
NAA38	ENST00000576861.5	TSL:3	c.-167+160G>T		intron	N/A	ENSP00000461545.1	I3L4V0

Frequencies

GnomAD3 genomes

AF:

0.00000682

AC:

AN:

146614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

8988

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1094096

Hom.:

Cov.:

AF XY:

0.00000576

AC XY:

AN XY:

521112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22750

American (AMR)

AF:

0.00

AC:

AN:

9904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14608

East Asian (EAS)

AF:

0.00

AC:

AN:

26436

South Asian (SAS)

AF:

0.0000442

AC:

AN:

22638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2968

European-Non Finnish (NFE)

AF:

0.00000324

AC:

AN:

925794

Other (OTH)

AF:

0.00

AC:

AN:

43714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.00000682

AC:

AN:

146614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71324

show subpopulations

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

African (AFR)

AF:

0.0000246

AC:

AN:

40624

American (AMR)

AF:

0.00

AC:

AN:

14806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

5000

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65888

Other (OTH)

AF:

0.00

AC:

AN:

2018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.89

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.48

M_CAP

Pathogenic

0.94

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.46

PhyloP100

2.0

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.36

REVEL

Benign

0.18

Sift

Uncertain

0.019

Sift4G

Benign

0.14

Vest4

0.13

MutPred

0.21

Gain of phosphorylation at P67 (P = 0.0021)

MVP

0.34

MPC

0.78

ClinPred

0.11

GERP RS

-0.17

PromoterAI

-0.0054

Neutral

(source)

gMVP

0.096

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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