rs548090628

Variant names:

• chr16-53156625-C-A
• rs548090628
• NM_001308319.2:c.536C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-53156625-C-A
• chr16-53156625-C-T

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001308319.2(CHD9):​c.536C>A​(p.Ser179*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHD9 NM_001308319.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• 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: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

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.536C>A	p.Ser179*	stop_gained	Exon 2 of 39	NP_001295248.1	Q3L8U1-1
	CHD9	NM_001382353.1		c.536C>A	p.Ser179*	stop_gained	Exon 2 of 39	NP_001369282.1	Q3L8U1-1
	CHD9	NM_001352127.3		c.536C>A	p.Ser179*	stop_gained	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.536C>A	p.Ser179*	stop_gained	Exon 2 of 39	ENSP00000396345.2	Q3L8U1-1
	CHD9	ENST00000398510.7	TSL:1	c.536C>A	p.Ser179*	stop_gained	Exon 1 of 38	ENSP00000381522.3	Q3L8U1-1
	CHD9	ENST00000564845.5	TSL:1	c.536C>A	p.Ser179*	stop_gained	Exon 2 of 39	ENSP00000455307.1	Q3L8U1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		3.0
Vest4		0.33
GERP RS		5.9

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: rs548090628; hg19: chr16-53190537;