Genetic Variant CHD9:p.Ser295Pro (chr16-53156972-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001308319.2(CHD9):c.883T>C(p.Ser295Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. S295A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CHD9
NM_001308319.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.491

Publications

0 publications found

Variant links:

Genes affected

CHD9 (HGNC:25701): (chromodomain helicase DNA binding protein 9) Predicted to enable ATP binding activity; ATP-dependent activity, acting on DNA; and DNA binding activity. Predicted to be involved in DNA duplex unwinding and chromatin organization. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CHD9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029104888).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308319.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD9	NM_001308319.2	MANE Select	c.883T>C	p.Ser295Pro	missense	Exon 2 of 39	NP_001295248.1	Q3L8U1-1
CHD9	NM_001382353.1		c.883T>C	p.Ser295Pro	missense	Exon 2 of 39	NP_001369282.1	Q3L8U1-1
CHD9	NM_001352127.3		c.883T>C	p.Ser295Pro	missense	Exon 2 of 39	NP_001339056.1	Q3L8U1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHD9	ENST00000447540.6	TSL:5 MANE Select	c.883T>C	p.Ser295Pro	missense	Exon 2 of 39	ENSP00000396345.2	Q3L8U1-1
CHD9	ENST00000398510.7	TSL:1	c.883T>C	p.Ser295Pro	missense	Exon 1 of 38	ENSP00000381522.3	Q3L8U1-1
CHD9	ENST00000564845.5	TSL:1	c.883T>C	p.Ser295Pro	missense	Exon 2 of 39	ENSP00000455307.1	Q3L8U1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460826

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53030

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111432

Other (OTH)

AF:

0.0000166

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.053

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.48

M_CAP

Benign

0.0095

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

PhyloP100

0.49

PrimateAI

Benign

0.30

PROVEAN

Benign

1.1

REVEL

Benign

0.19

Sift

Benign

0.45

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.052

MutPred

0.088

Gain of loop (P = 0.0312)

MVP

0.22

MPC

0.073

ClinPred

0.044

GERP RS

2.6

Varity_R

0.084

gMVP

0.38

Mutation Taster

=95/5

polymorphism

(source)

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