5-56909667-G-C

Variant names:

• chr5-56909667-G-C
• rs779728809
• NM_153706.4:c.22G>C

Variant summary

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

The NM_153706.4(SETD9):​c.22G>C​(p.Gly8Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,188 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G8S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SETD9 NM_153706.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.95
• Publications: 0 publications found

Genes affected

SETD9 (HGNC:28508): (SET domain containing 9) Predicted to enable lysine N-methyltransferase activity. Predicted to be involved in regulation of signal transduction by p53 class mediator. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000225230 (HGNC:):

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=0.13733655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153706.4. 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
	SETD9	NM_153706.4	MANE Select	c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	NP_714917.2	Q8NE22-1
	SETD9	NM_001171990.3		c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	NP_001165461.1	Q8NE22-2
	SETD9	NM_001323019.2		c.22G>C	p.Gly8Arg	missense	Exon 1 of 4	NP_001309948.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD9	ENST00000285947.5	TSL:1 MANE Select	c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	ENSP00000285947.2	Q8NE22-1
	SETD9	ENST00000628593.1	TSL:1	c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	ENSP00000486609.1	Q8NE22-2
	SETD9	ENST00000918990.1		c.22G>C	p.Gly8Arg	missense	Exon 1 of 6	ENSP00000589049.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724970

African (AFR) AF: 0.0000306 AC: 1 AN: 32688

American (AMR) AF: 0.00 AC: 0 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39286

South Asian (SAS) AF: 0.00 AC: 0 AN: 85748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110430

Other (OTH) AF: 0.00 AC: 0 AN: 60206

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
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.82
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.021
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		5.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.035
Sift	Benign	0.60	T
Sift4G	Benign	0.54	T
Polyphen		0.0050	B
Vest4		0.33
MutPred		0.26		Gain of solvent accessibility (P = 0.1319)
MVP		0.35
MPC		0.24
ClinPred		0.44	T
GERP RS		5.0
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.32
Mutation Taster		=91/9	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: rs779728809; hg19: chr5-56205494;