rs3830028

Positions:

• chrX-153059569-T-C

Variant summary

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

The NM_013364.6(PNMA3):​c.*1122T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.93 (34065 hom., 30987 hem., cov: 23)
  • Exomes 𝑓: 0.98 (3747 hom. 3493 hem.)
  • Failed GnomAD Quality Control
• Consequence: PNMA3 NM_013364.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.00

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=-0.93).
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNMA3	NM_013364.6	c.*1122T>C		3_prime_UTR_variant	2/2	ENST00000593810.3
PNMA3	NM_001282535.2	c.*1025T>C		3_prime_UTR_variant	3/3
PNMA3	XR_938508.4	n.2277T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNMA3	ENST00000593810.3	c.*1122T>C		3_prime_UTR_variant	2/2		NM_013364.6	P1
PNMA3	ENST00000619635.1	c.*1025T>C		3_prime_UTR_variant	3/3	1
PNMA3	ENST00000424805.1	c.*610T>C		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.931 AC: 103475 AN: 111090 Hom.: 34070 Cov.: 23 AF XY: 0.930 AC XY: 30933 AN XY: 33272

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.949

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.932

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.904

GnomAD4 exome AF: 0.977 AC: 11164 AN: 11431 Hom.: 3747 Cov.: 0 AF XY: 0.978 AC XY: 3493 AN XY: 3573

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.667

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.977

Gnomad4 NFE exome AF: 0.954

Gnomad4 OTH exome AF: 0.958

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.931 AC: 103516 AN: 111144 Hom.: 34065 Cov.: 23 AF XY: 0.930 AC XY: 30987 AN XY: 33336

Gnomad4 AFR AF: 0.963

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.956

Gnomad4 OTH AF: 0.906

Alfa AF: 0.946 Hom.: 8556

Bravo AF: 0.912

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3830028; hg19: chrX-152227929;