16-53156600-C-A

Variant names:

• chr16-53156600-C-A
• rs2041538602
• NM_001308319.2:c.511C>A

Variant summary

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

The NM_001308319.2(CHD9):​c.511C>A​(p.Gln171Lys) 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. 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: 5.79

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

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=0.26370507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHD9	NM_001308319.2	c.511C>A	p.Gln171Lys	missense_variant	Exon 2 of 39	ENST00000447540.6	NP_001295248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHD9	ENST00000447540.6	c.511C>A	p.Gln171Lys	missense_variant	Exon 2 of 39	5	NM_001308319.2	ENSP00000396345.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.511C>A (p.Q171K) alteration is located in exon 2 (coding exon 1) of the CHD9 gene. This alteration results from a C to A substitution at nucleotide position 511, causing the glutamine (Q) at amino acid position 171 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	0.086
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;.;T;.;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D;.;D;D;.
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Benign	1.0	L;L;.;L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Uncertain	0.35
Sift	Uncertain	0.018	D;D;D;D;D
Sift4G	Uncertain	0.051	T;D;T;D;T
Polyphen		0.034	B;B;.;B;B
Vest4		0.30
MutPred		0.25		Gain of ubiquitination at Q171 (P = 0.0045);Gain of ubiquitination at Q171 (P = 0.0045);Gain of ubiquitination at Q171 (P = 0.0045);Gain of ubiquitination at Q171 (P = 0.0045);Gain of ubiquitination at Q171 (P = 0.0045);
MVP		0.66
MPC		0.21
ClinPred		0.66	D
GERP RS		5.9
Varity_R		0.19
gMVP		0.58

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: rs2041538602; hg19: chr16-53190512;