5-56916898-G-T

Variant names:

• chr5-56916898-G-T
• rs746822110
• NM_153706.4:c.896G>T

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.896G>T​(p.Ser299Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SETD9 NM_153706.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91
• 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]

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=0.17704156).

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.896G>T	p.Ser299Ile	missense	Exon 6 of 6	NP_714917.2	Q8NE22-1
	SETD9	NM_001323018.2		c.818G>T	p.Ser273Ile	missense	Exon 6 of 6	NP_001309947.1
	SETD9	NM_001323022.1		c.440G>T	p.Ser147Ile	missense	Exon 6 of 6	NP_001309951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETD9	ENST00000285947.5	TSL:1 MANE Select	c.896G>T	p.Ser299Ile	missense	Exon 6 of 6	ENSP00000285947.2	Q8NE22-1
	SETD9	ENST00000628593.1	TSL:1	c.812+1932G>T		intron	N/A	ENSP00000486609.1	Q8NE22-2
	SETD9	ENST00000918990.1		c.863G>T	p.Ser288Ile	missense	Exon 6 of 6	ENSP00000589049.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444382 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717348

African (AFR) AF: 0.00 AC: 0 AN: 32880

American (AMR) AF: 0.00 AC: 0 AN: 41086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25932

East Asian (EAS) AF: 0.00 AC: 0 AN: 39036

South Asian (SAS) AF: 0.00 AC: 0 AN: 80394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106260

Other (OTH) AF: 0.0000167 AC: 1 AN: 59826

GnomAD4 genome Cov.: 32

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	Pathogenic	0.57
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.030
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.021	D
Polyphen		0.50	P
Vest4		0.27
MutPred		0.37		Loss of disorder (P = 1e-04)
MVP		0.35
MPC		0.41
ClinPred		0.63	D
GERP RS		0.50
Varity_R		0.17
gMVP		0.48
Mutation Taster		=92/8	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: rs746822110; hg19: chr5-56212725;