chr9-69723396-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099666.2(PTAR1):​c.877G>A​(p.Glu293Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PTAR1
NM_001099666.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33
Variant links:
Genes affected
PTAR1 (HGNC:30449): (protein prenyltransferase alpha subunit repeat containing 1) Predicted to enable protein prenyltransferase activity. Predicted to be involved in protein prenylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2023176).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTAR1NM_001099666.2 linkc.877G>A p.Glu293Lys missense_variant Exon 6 of 8 ENST00000340434.5 NP_001093136.1 Q7Z6K3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTAR1ENST00000340434.5 linkc.877G>A p.Glu293Lys missense_variant Exon 6 of 8 1 NM_001099666.2 ENSP00000344299.4 Q7Z6K3
PTAR1ENST00000377200.9 linkc.640G>A p.Glu214Lys missense_variant Exon 4 of 5 1 ENSP00000366405.5 X6R9N0
PTAR1ENST00000415701.6 linkc.175G>A p.Glu59Lys missense_variant Exon 1 of 3 3 ENSP00000405943.2 J3KQP8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 27, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.877G>A (p.E293K) alteration is located in exon 6 (coding exon 6) of the PTAR1 gene. This alteration results from a G to A substitution at nucleotide position 877, causing the glutamic acid (E) at amino acid position 293 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.010
.;T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.6
.;L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.11
Sift
Benign
0.35
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.0030
.;B
Vest4
0.32
MutPred
0.51
.;Gain of methylation at E293 (P = 0.0189);
MVP
0.15
MPC
0.35
ClinPred
0.32
T
GERP RS
6.0
Varity_R
0.18
gMVP
0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-72338312; API