rs2257505

Variant names:

• chr5-56911296-T-A
• rs2257505
• NM_153706.4:c.226T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-56911296-T-A
• chr5-56911296-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153706.4(SETD9):​c.226T>A​(p.Ser76Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,611,678 control chromosomes in the GnomAD database, including 419,561 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (32134 hom., cov: 32)
  • Exomes 𝑓: 0.72 (387427 hom.)
• Consequence: SETD9 NM_153706.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 49 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6553838E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SETD9	NM_153706.4	c.226T>A	p.Ser76Thr	missense_variant	Exon 2 of 6	ENST00000285947.5	NP_714917.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SETD9	ENST00000285947.5	c.226T>A	p.Ser76Thr	missense_variant	Exon 2 of 6	1	NM_153706.4	ENSP00000285947.2

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96001 AN: 151978 Hom.: 32124 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.666

GnomAD2 exomes AF: 0.628 AC: 156517 AN: 249246 AF XY: 0.639

Gnomad AFR exome AF: 0.472

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.772

Gnomad EAS exome AF: 0.224

Gnomad FIN exome AF: 0.754

Gnomad NFE exome AF: 0.755

Gnomad OTH exome AF: 0.677

GnomAD4 exome AF: 0.719 AC: 1049352 AN: 1459582 Hom.: 387427 Cov.: 50 AF XY: 0.716 AC XY: 519475 AN XY: 726024

African (AFR) AF: 0.474 AC: 15791 AN: 33336

American (AMR) AF: 0.456 AC: 20202 AN: 44330

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 20126 AN: 26024

East Asian (EAS) AF: 0.266 AC: 10543 AN: 39676

South Asian (SAS) AF: 0.547 AC: 46909 AN: 85750

European-Finnish (FIN) AF: 0.755 AC: 40289 AN: 53350

Middle Eastern (MID) AF: 0.710 AC: 4085 AN: 5752

European-Non Finnish (NFE) AF: 0.765 AC: 849998 AN: 1111078

Other (OTH) AF: 0.687 AC: 41409 AN: 60286

GnomAD4 genome AF: 0.631 AC: 96046 AN: 152096 Hom.: 32134 Cov.: 32 AF XY: 0.624 AC XY: 46391 AN XY: 74342

African (AFR) AF: 0.473 AC: 19595 AN: 41460

American (AMR) AF: 0.535 AC: 8181 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2658 AN: 3472

East Asian (EAS) AF: 0.248 AC: 1287 AN: 5180

South Asian (SAS) AF: 0.528 AC: 2542 AN: 4818

European-Finnish (FIN) AF: 0.747 AC: 7906 AN: 10586

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51693 AN: 67984

Other (OTH) AF: 0.661 AC: 1395 AN: 2112

Alfa AF: 0.726 Hom.: 30889

Bravo AF: 0.609

TwinsUK AF: 0.773 AC: 2868

ALSPAC AF: 0.765 AC: 2947

ESP6500AA AF: 0.479 AC: 2110

ESP6500EA AF: 0.758 AC: 6521

ExAC AF: 0.631 AC: 76656

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.77
DEOGEN2	Benign	0.0078	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.042	T;T
MetaRNN	Benign	0.0000017	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N;N
PhyloP100		-0.061
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.080	N;.
REVEL	Benign	0.019
Sift	Benign	1.0	T;.
Sift4G	Benign	0.70	T;T
Polyphen		0.0	B;.
Vest4		0.042
MPC		0.18
ClinPred		0.0015	T
GERP RS		1.5
Varity_R		0.041
gMVP		0.13
Mutation Taster		=99/1	polymorphism (auto)

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: rs2257505; hg19: chr5-56207123; COSMIC: COSV53650424; COSMIC: COSV53650424;