chr16-53156298-A-C

Position:

• chr16-53156298-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308319.2(CHD9):​c.209A>C​(p.Gln70Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD9 NM_001308319.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.32

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16042969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHD9	NM_001308319.2	c.209A>C	p.Gln70Pro	missense_variant	2/39	ENST00000447540.6	NP_001295248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHD9	ENST00000447540.6	c.209A>C	p.Gln70Pro	missense_variant	2/39	5	NM_001308319.2	ENSP00000396345.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.209A>C (p.Q70P) alteration is located in exon 2 (coding exon 1) of the CHD9 gene. This alteration results from a A to C substitution at nucleotide position 209, causing the glutamine (Q) at amino acid position 70 to be replaced by a proline (P). 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	0.066
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.042	T;.;T;.;T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.78	T;.;T;T;.
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N;N;.;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.71	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.0	B;B;.;B;B
Vest4		0.34
MutPred		0.35		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.58
MPC		0.071
ClinPred		0.16	T
GERP RS		4.7
Varity_R		0.40
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

Other links and lift over

dbSNP: rs2041515867; hg19: chr16-53190210;