X-153058013-CCT-GCA

Variant names:

• chrX-153058013-CCT-GCA
• NM_013364.6:c.958_960delCCTinsGCA
• PNMA3 p.Pro320Ala

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_013364.6(PNMA3):​c.958_960delCCTinsGCA​(p.Pro320Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. P320T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: PNMA3 NM_013364.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 0 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 0 ACMG points.

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.958_960delCCTinsGCA	p.Pro320Ala	missense	N/A	NP_037496.4	Q9UL41-1
	PNMA3	NM_001282535.2		c.958_960delCCTinsGCA	p.Pro320Ala	missense	N/A	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.958_960delCCTinsGCA	p.Pro320Ala	missense	N/A	ENSP00000469445.1	Q9UL41-1
	PNMA3	ENST00000619635.1	TSL:1	c.958_960delCCTinsGCA	p.Pro320Ala	missense	N/A	ENSP00000480719.1	Q9UL41-2
	PNMA3	ENST00000424805.1	TSL:5	n.958_960delCCTinsGCA		non_coding_transcript_exon	Exon 2 of 3	ENSP00000390576.1	Q9UL41-1

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-152226370;