rs1036811244

Variant summary

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

The NM_013364.6(PNMA3):​c.1024C>A​(p.Pro342Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 112,554 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. P342A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Consequence

PNMA3
NM_013364.6 missense

Scores

14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.558
Variant links:
Genes affected
PNMA3 (HGNC:18742): (PNMA family member 3) The protein encoded by this gene belongs to the paraneoplastic antigen MA (PNMA) family, which shares homology with retroviral Gag proteins. The PNMA antigens are highly expressed in the brain and also in a range of tumors associated with serious neurological phenotypes. PMID:16407312 reports the presence of a functional -1 ribosomal frameshift signal (consisting of a heptanucleotide shift motif followed 3' by a pseudoknot structure) in this gene, however, the frame-shifted product has not been characterized. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 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 rank MANE Protein UniProt
PNMA3NM_013364.6 linkc.1024C>A p.Pro342Thr missense_variant Exon 2 of 2 ENST00000593810.3 NP_037496.4 Q9UL41-1
PNMA3NM_001282535.2 linkc.1024C>A p.Pro342Thr missense_variant Exon 2 of 3 NP_001269464.1 Q9UL41-2
PNMA3XR_938508.4 linkn.1299C>A non_coding_transcript_exon_variant Exon 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PNMA3ENST00000593810.3 linkc.1024C>A p.Pro342Thr missense_variant Exon 2 of 2 6 NM_013364.6 ENSP00000469445.1 Q9UL41-1
PNMA3ENST00000619635.1 linkc.1024C>A p.Pro342Thr missense_variant Exon 2 of 3 1 ENSP00000480719.1 Q9UL41-2
PNMA3ENST00000424805.1 linkn.1024C>A non_coding_transcript_exon_variant Exon 2 of 3 5 ENSP00000390576.1 Q9UL41-1

Frequencies

GnomAD3 genomes
AF:
0.00000888
AC:
1
AN:
112554
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34694
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
AF:
0.00000888
AC:
1
AN:
112554
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34694
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
8.6
DANN
Benign
0.11
DEOGEN2
Benign
0.026
.;T
FATHMM_MKL
Benign
0.0071
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.053
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.81
L;L
PrimateAI
Benign
0.41
T
Sift4G
Benign
0.56
T;T
Polyphen
0.038
.;B
Vest4
0.098
MutPred
0.24
Gain of phosphorylation at P342 (P = 0.0228);Gain of phosphorylation at P342 (P = 0.0228);
MVP
0.061
ClinPred
0.020
T
GERP RS
-0.069
Varity_R
0.045
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.28
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.28
Position offset: -3

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: rs1036811244; hg19: chrX-152226436; API