dbSNP rs1036811244: PNMA3:p.Pro342Thr (chrX-153058079-C-A) – ACMG Classification: Uncertain_significance (2 pts)

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

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]

PNMA3 links:

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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
PNMA3	NM_013364.6 link	c.1024C>A	p.Pro342Thr	missense_variant	Exon 2 of 2	ENST00000593810.3	NP_037496.4	Q9UL41-1
PNMA3	NM_001282535.2 link	c.1024C>A	p.Pro342Thr	missense_variant	Exon 2 of 3		NP_001269464.1	Q9UL41-2
PNMA3	XR_938508.4 link	n.1299C>A		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PNMA3	ENST00000593810.3 link	c.1024C>A	p.Pro342Thr	missense_variant	Exon 2 of 2	6	NM_013364.6	ENSP00000469445.1	Q9UL41-1
PNMA3	ENST00000619635.1 link	c.1024C>A	p.Pro342Thr	missense_variant	Exon 2 of 3	1		ENSP00000480719.1	Q9UL41-2
PNMA3	ENST00000424805.1 link	n.1024C>A		non_coding_transcript_exon_variant	Exon 2 of 3	5		ENSP00000390576.1	Q9UL41-1

Frequencies

GnomAD3 genomes

AF:

0.00000888

AC:

AN:

112554

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

GnomAD4 genome

AF:

0.00000888

AC:

AN:

112554

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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

BayesDel_noAF

Benign

-1.0

CADD

Benign

8.6

DANN

Benign

0.11

DEOGEN2

Benign

0.026

.;T

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.053

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.41

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over