Genetic Variant SETD9:p.Tyr37Cys (chr5-56911180-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153706.4(SETD9):c.110A>G(p.Tyr37Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000104 in 1,543,028 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SETD9
NM_153706.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36

Publications

0 publications found

Variant links:

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]

SETD9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1298846).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETD9	NM_153706.4	MANE Select	c.110A>G	p.Tyr37Cys	missense	Exon 2 of 6	NP_714917.2	Q8NE22-1
SETD9	NM_001323018.2		c.32A>G	p.Tyr11Cys	missense	Exon 2 of 6	NP_001309947.1
SETD9	NM_001171990.3		c.110A>G	p.Tyr37Cys	missense	Exon 2 of 6	NP_001165461.1	Q8NE22-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SETD9	ENST00000285947.5	TSL:1 MANE Select	c.110A>G	p.Tyr37Cys	missense	Exon 2 of 6	ENSP00000285947.2	Q8NE22-1
SETD9	ENST00000628593.1	TSL:1	c.110A>G	p.Tyr37Cys	missense	Exon 2 of 6	ENSP00000486609.1	Q8NE22-2
SETD9	ENST00000918990.1		c.110A>G	p.Tyr37Cys	missense	Exon 2 of 6	ENSP00000589049.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000316

AC:

AN:

190132

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000370

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1390688

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

686268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30810

American (AMR)

AF:

0.00

AC:

AN:

31302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21054

East Asian (EAS)

AF:

0.000255

AC:

AN:

39280

South Asian (SAS)

AF:

0.00

AC:

AN:

72960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5414

European-Non Finnish (NFE)

AF:

0.00000370

AC:

AN:

1081970

Other (OTH)

AF:

0.00

AC:

AN:

57354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000359

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.015

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PhyloP100

4.4

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.9

REVEL

Benign

0.098

Sift

Benign

0.14

Sift4G

Benign

0.17

Polyphen

0.98

Vest4

0.59

MVP

0.40

MPC

0.82

ClinPred

0.21

GERP RS

4.3

Varity_R

0.11

gMVP

0.27

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over