chr14-35312899-T-C

Variant summary

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

The NM_002791.3(PSMA6):ā€‹c.428T>Cā€‹(p.Ile143Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PSMA6
NM_002791.3 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.21
Variant links:
Genes affected
PSMA6 (HGNC:9535): (proteasome 20S subunit alpha 6) The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. Multiple transcript variants encoding several different isoforms have been found for this gene. A pseudogene has been identified on the Y chromosome. [provided by RefSeq, Aug 2013]

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/exons MANE Protein UniProt
PSMA6NM_002791.3 linkuse as main transcriptc.428T>C p.Ile143Thr missense_variant 5/7 ENST00000261479.9 NP_002782.1 P60900-1A0A140VK44

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSMA6ENST00000261479.9 linkuse as main transcriptc.428T>C p.Ile143Thr missense_variant 5/71 NM_002791.3 ENSP00000261479.4 P60900-1
ENSG00000258790ENST00000557565.1 linkuse as main transcriptn.*1243T>C non_coding_transcript_exon_variant 13/152 ENSP00000454657.1
ENSG00000258790ENST00000557565.1 linkuse as main transcriptn.*1243T>C 3_prime_UTR_variant 13/152 ENSP00000454657.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1439060
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
716476
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 24, 2023The c.428T>C (p.I143T) alteration is located in exon 5 (coding exon 5) of the PSMA6 gene. This alteration results from a T to C substitution at nucleotide position 428, causing the isoleucine (I) at amino acid position 143 to be replaced by a threonine (T). 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
0.30
BayesDel_addAF
Uncertain
0.017
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
.;.;T;T;.;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
D;D;D;D;.;D
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.67
D;D;D;D;D;D
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.0
.;.;M;.;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.8
N;.;N;N;N;N
REVEL
Benign
0.21
Sift
Benign
0.077
T;.;T;T;T;D
Sift4G
Benign
0.15
T;T;T;T;T;T
Polyphen
0.0020
.;.;B;.;.;.
Vest4
0.72
MutPred
0.70
.;.;Loss of stability (P = 2e-04);.;.;Loss of stability (P = 2e-04);
MVP
0.41
MPC
0.93
ClinPred
0.80
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr14-35782105; API