rs1384979905

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153706.4(SETD9):​c.437C>G​(p.Pro146Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P146L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

SETD9
NM_153706.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SETD9NM_153706.4 linkc.437C>G p.Pro146Arg missense_variant Exon 2 of 6 ENST00000285947.5 NP_714917.2 Q8NE22-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SETD9ENST00000285947.5 linkc.437C>G p.Pro146Arg missense_variant Exon 2 of 6 1 NM_153706.4 ENSP00000285947.2 Q8NE22-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000451
AC:
1
AN:
221756
Hom.:
0
AF XY:
0.00000833
AC XY:
1
AN XY:
120038
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000405
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1433498
Hom.:
0
Cov.:
33
AF XY:
0.00000140
AC XY:
1
AN XY:
711840
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000246
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.095
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.33
CADD
Pathogenic
27
DANN
Benign
0.97
DEOGEN2
Benign
0.16
T;.
Eigen
Benign
0.014
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-5.0
D;.
REVEL
Benign
0.10
Sift
Benign
0.13
T;.
Sift4G
Benign
0.22
T;T
Polyphen
0.23
B;.
Vest4
0.29
MutPred
0.47
Gain of MoRF binding (P = 0.0021);Gain of MoRF binding (P = 0.0021);
MVP
0.36
MPC
0.24
ClinPred
0.67
D
GERP RS
4.5
Varity_R
0.40
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.85
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.85
Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1384979905; hg19: chr5-56207334; API