chr16-53209530-C-A

Variant names:

• chr16-53209530-C-A
• NM_001308319.2:c.1501C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001308319.2(CHD9):​c.1501C>A​(p.Gln501Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD9 NM_001308319.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

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]

ACMG classification

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=0.1796673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD9	NM_001308319.2	c.1501C>A	p.Gln501Lys	missense_variant	Exon 3 of 39	ENST00000447540.6	NP_001295248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD9	ENST00000447540.6	c.1501C>A	p.Gln501Lys	missense_variant	Exon 3 of 39	5	NM_001308319.2	ENSP00000396345.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1501C>A (p.Q501K) alteration is located in exon 3 (coding exon 2) of the CHD9 gene. This alteration results from a C to A substitution at nucleotide position 1501, causing the glutamine (Q) at amino acid position 501 to be replaced by a lysine (K). 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	0.090
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.041	T;.;T;.;T;T
Eigen	Benign	-0.031
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;.;D;D;.;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.18	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;.;L;L;.
PhyloP100		3.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.52	N;N;N;N;N;N
REVEL	Benign	0.082
Sift	Uncertain	0.018	D;D;D;D;D;D
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.039	B;B;.;B;B;.
Vest4		0.49
MutPred		0.22		Gain of ubiquitination at Q501 (P = 0.009);Gain of ubiquitination at Q501 (P = 0.009);Gain of ubiquitination at Q501 (P = 0.009);Gain of ubiquitination at Q501 (P = 0.009);Gain of ubiquitination at Q501 (P = 0.009);.;
MVP		0.47
MPC		0.097
ClinPred		0.57	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

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Other links and lift over

hg19: chr16-53243442;