chr9-76638226-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015225.3(PRUNE2):āc.8791A>Cā(p.Ser2931Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,792 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 (ā ).
Frequency
Genomes: š 0.00016 ( 0 hom., cov: 32)
Exomes š: 0.000017 ( 0 hom. )
Consequence
PRUNE2
NM_015225.3 missense
NM_015225.3 missense
Scores
1
11
7
Clinical Significance
Conservation
PhyloP100: 2.82
Genes affected
PRUNE2 (HGNC:25209): (prune homolog 2 with BCH domain) The protein encoded by this gene belongs to the B-cell CLL/lymphoma 2 and adenovirus E1B 19 kDa interacting family, whose members play roles in many cellular processes including apotosis, cell transformation, and synaptic function. Several functions for this protein have been demonstrated including suppression of Ras homolog family member A activity, which results in reduced stress fiber formation and suppression of oncogenic cellular transformation. A high molecular weight isoform of this protein has also been shown to colocalize with Adaptor protein complex 2, beta-Adaptin and endodermal markers, suggesting an involvement in post-endocytic trafficking. In prostate cancer cells, this gene acts as a tumor suppressor and its expression is regulated by prostate cancer antigen 3, a non-protein coding gene on the opposite DNA strand in an intron of this gene. Prostate cancer antigen 3 regulates levels of this gene through formation of a double-stranded RNA that undergoes adenosine deaminase actin on RNA-dependent adenosine-to-inosine RNA editing. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]
GCNT1 (HGNC:4203): (glucosaminyl (N-acetyl) transferase 1) This gene is a member of the beta-1,6-N-acetylglucosaminyltransferase gene family. It is essential to the formation of Gal beta 1-3(GlcNAc beta 1-6)GalNAc structures and the core 2 O-glycan branch. The gene coding this enzyme was originally mapped to 9q21, but was later localized to 9q13. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]
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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=0.08139753).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRUNE2 | NM_015225.3 | c.8791A>C | p.Ser2931Arg | missense_variant | 13/19 | ENST00000376718.8 | |
LOC105376095 | XR_007061586.1 | n.921-3968T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRUNE2 | ENST00000376718.8 | c.8791A>C | p.Ser2931Arg | missense_variant | 13/19 | 5 | NM_015225.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152244Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248296Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134908
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461430Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 727004
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GnomAD4 genome AF: 0.000164 AC: 25AN: 152362Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74510
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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 submitter | clinical testing | Ambry Genetics | May 30, 2024 | The c.8791A>C (p.S2931R) alteration is located in exon 13 (coding exon 13) of the PRUNE2 gene. This alteration results from a A to C substitution at nucleotide position 8791, causing the serine (S) at amino acid position 2931 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
.;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;N;.;N;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;.;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;.;.
Vest4
MutPred
0.39
.;.;Gain of glycosylation at S2930 (P = 0.0909);.;.;.;
MVP
MPC
0.46
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at