rs1045069

Positions:

• chrX-153060001-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013364.6(PNMA3):​c.*1554G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 123,831 control chromosomes in the GnomAD database, including 5,765 homozygotes. There are 12,356 hemizygotes 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.

• Frequency:
  • Genomes: 𝑓 0.32 (4889 hom., 10707 hem., cov: 25)
  • Exomes 𝑓: 0.47 (876 hom. 1649 hem.)
• Consequence: PNMA3 NM_013364.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNMA3	NM_013364.6	c.*1554G>A		3_prime_UTR_variant	2/2	ENST00000593810.3	NP_037496.4
PNMA3	NM_001282535.2	c.*1457G>A		3_prime_UTR_variant	3/3		NP_001269464.1
PNMA3	XR_938508.4	n.2709G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNMA3	ENST00000593810.3	c.*1554G>A		3_prime_UTR_variant	2/2		NM_013364.6	ENSP00000469445	P1
PNMA3	ENST00000619635.1	c.*1457G>A		3_prime_UTR_variant	3/3	1		ENSP00000480719
PNMA3	ENST00000424805.1	c.*1042G>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	5		ENSP00000390576

Frequencies

GnomAD3 genomes AF: 0.325 AC: 36455 AN: 112329 Hom.: 4893 Cov.: 25 AF XY: 0.310 AC XY: 10706 AN XY: 34515

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.466 AC: 5338 AN: 11448 Hom.: 876 Cov.: 0 AF XY: 0.464 AC XY: 1649 AN XY: 3556

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.324 AC: 36443 AN: 112383 Hom.: 4889 Cov.: 25 AF XY: 0.310 AC XY: 10707 AN XY: 34579

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.00196

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.274

Alfa AF: 0.413 Hom.: 22439

Bravo AF: 0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.61
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1045069; hg19: chrX-152228361; COSMIC: COSV64722386; COSMIC: COSV64722386;