Genetic Variant CHD9:p.Asn327Ser (chr16-53157069-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001308319.2(CHD9):c.980A>G(p.Asn327Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,612,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CHD9
NM_001308319.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061615646).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD9	NM_001308319.2 link	c.980A>G	p.Asn327Ser	missense_variant	Exon 2 of 39	ENST00000447540.6	NP_001295248.1	Q3L8U1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD9	ENST00000447540.6 link	c.980A>G	p.Asn327Ser	missense_variant	Exon 2 of 39	5	NM_001308319.2	ENSP00000396345.2		Q3L8U1-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

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

GnomAD3 exomes

AF:

0.0000807

AC:

AN:

247936

Hom.:

AF XY:

0.0000966

AC XY:

AN XY:

134578

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00111

Gnomad SAS 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:

0.0000130

AC:

AN:

1460840

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.980A>G (p.N327S) alteration is located in exon 2 (coding exon 1) of the CHD9 gene. This alteration results from a A to G substitution at nucleotide position 980, causing the asparagine (N) at amino acid position 327 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.046

T;.;T;.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;.;D;D;.

M_CAP

Benign

0.024

MetaRNN

Benign

0.062

T;T;T;T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

0.90

L;L;.;L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.76

N;N;N;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.053

T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T

Polyphen

0.99

D;D;.;D;D

Vest4

0.48

MutPred

0.26

Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);

MVP

0.69

MPC

0.074

ClinPred

0.19

GERP RS

6.0

Varity_R

0.11

gMVP

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over