chr16-53156969-G-C

Variant names:

• chr16-53156969-G-C
• rs765814836
• NM_001308319.2:c.880G>C

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.880G>C​(p.Ala294Pro) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A294G) has been classified 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: 0.968
• Publications: 0 publications found

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=0.13592955).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD9	NM_001308319.2	MANE Select	c.880G>C	p.Ala294Pro	missense	Exon 2 of 39	NP_001295248.1	Q3L8U1-1
	CHD9	NM_001382353.1		c.880G>C	p.Ala294Pro	missense	Exon 2 of 39	NP_001369282.1	Q3L8U1-1
	CHD9	NM_001352127.3		c.880G>C	p.Ala294Pro	missense	Exon 2 of 39	NP_001339056.1	Q3L8U1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHD9	ENST00000447540.6	TSL:5 MANE Select	c.880G>C	p.Ala294Pro	missense	Exon 2 of 39	ENSP00000396345.2	Q3L8U1-1
	CHD9	ENST00000398510.7	TSL:1	c.880G>C	p.Ala294Pro	missense	Exon 1 of 38	ENSP00000381522.3	Q3L8U1-1
	CHD9	ENST00000564845.5	TSL:1	c.880G>C	p.Ala294Pro	missense	Exon 2 of 39	ENSP00000455307.1	Q3L8U1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248572 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.088
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.97
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.38	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.18	T
Polyphen		0.61	P
Vest4		0.16
MutPred		0.14		Gain of loop (P = 0.0166)
MVP		0.65
MPC		0.24
ClinPred		0.31	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.55

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

Other links and lift over

dbSNP: rs765814836; hg19: chr16-53190881;