chr16-53156795-A-G

Variant names:

• chr16-53156795-A-G
• rs377416139
• NM_001308319.2:c.706A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001308319.2(CHD9):​c.706A>G​(p.Asn236Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CHD9 NM_001308319.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.77
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26680064).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.706A>G	p.Asn236Asp	missense	Exon 2 of 39	NP_001295248.1	Q3L8U1-1
	CHD9	NM_001382353.1		c.706A>G	p.Asn236Asp	missense	Exon 2 of 39	NP_001369282.1	Q3L8U1-1
	CHD9	NM_001352127.3		c.706A>G	p.Asn236Asp	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.706A>G	p.Asn236Asp	missense	Exon 2 of 39	ENSP00000396345.2	Q3L8U1-1
	CHD9	ENST00000398510.7	TSL:1	c.706A>G	p.Asn236Asp	missense	Exon 1 of 38	ENSP00000381522.3	Q3L8U1-1
	CHD9	ENST00000564845.5	TSL:1	c.706A>G	p.Asn236Asp	missense	Exon 2 of 39	ENSP00000455307.1	Q3L8U1-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461544 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727048

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.00000827 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.96	N
REVEL	Uncertain	0.32
Sift	Benign	0.038	D
Sift4G	Benign	0.63	T
Polyphen		0.016	B
Vest4		0.20
MVP		0.75
MPC		0.11
ClinPred		0.16	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.35
Mutation Taster		=93/7	polymorphism

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: rs377416139; hg19: chr16-53190707;