X-153058079-C-A

Variant names:

• chrX-153058079-C-A
• rs1036811244
• NM_013364.6:c.1024C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013364.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNMA3	NM_013364.6	MANE Select	c.1024C>A	p.Pro342Thr	missense	Exon 2 of 2	NP_037496.4	Q9UL41-1
	PNMA3	NM_001282535.2		c.1024C>A	p.Pro342Thr	missense	Exon 2 of 3	NP_001269464.1	Q9UL41-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNMA3	ENST00000593810.3	TSL:6 MANE Select	c.1024C>A	p.Pro342Thr	missense	Exon 2 of 2	ENSP00000469445.1	Q9UL41-1
	PNMA3	ENST00000619635.1	TSL:1	c.1024C>A	p.Pro342Thr	missense	Exon 2 of 3	ENSP00000480719.1	Q9UL41-2
	PNMA3	ENST00000424805.1	TSL:5	n.1024C>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000390576.1	Q9UL41-1

Frequencies

GnomAD3 genomes AF: 0.00000888 AC: 1 AN: 112554 Hom.: 0 Cov.: 24

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

African (AFR) AF: 0.00 AC: 0 AN: 30993

American (AMR) AF: 0.00 AC: 0 AN: 10770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2689

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6217

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53229

Other (OTH) AF: 0.00 AC: 0 AN: 1528

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.56
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.56	T
Polyphen		0.038	B
Vest4		0.098
MutPred		0.24		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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1036811244; hg19: chrX-152226436;