dbSNP rs1045069: PNMA3:c.*1554G>A (chrX-153060001-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.827

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
PNMA3	NM_013364.6 link	c.*1554G>A	3_prime_UTR_variant	Exon 2 of 2	ENST00000593810.3	NP_037496.4
PNMA3	XR_938508.4 link	n.2709G>A	non_coding_transcript_exon_variant	Exon 3 of 3
PNMA3	NM_001282535.2 link	c.*1457G>A	3_prime_UTR_variant	Exon 3 of 3		NP_001269464.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PNMA3	ENST00000593810.3 link	c.*1554G>A	3_prime_UTR_variant	Exon 2 of 2	6	NM_013364.6	ENSP00000469445.1
PNMA3	ENST00000619635.1 link	c.*1457G>A	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000480719.1
PNMA3	ENST00000424805.1 link	n.*1042G>A	non_coding_transcript_exon_variant	Exon 3 of 3	5		ENSP00000390576.1
PNMA3	ENST00000424805.1 link	n.*1042G>A	3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000390576.1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

36455

AN:

112329

Hom.:

4893

Cov.:

show subpopulations

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.:

AF XY:

0.464

AC XY:

1649

AN XY:

3556

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.467

AC:

5227

AN:

11189

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.464

AC:

AN:

166

Other (OTH)

AF:

0.410

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

111

222

334

445

556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.324

AC:

36443

AN:

112383

Hom.:

4889

Cov.:

AF XY:

0.310

AC XY:

10707

AN XY:

34579

show subpopulations

African (AFR)

AF:

0.202

AC:

6264

AN:

31053

American (AMR)

AF:

0.217

AC:

2341

AN:

10794

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1124

AN:

2644

East Asian (EAS)

AF:

0.00196

AC:

AN:

3580

South Asian (SAS)

AF:

0.122

AC:

338

AN:

2766

European-Finnish (FIN)

AF:

0.461

AC:

2817

AN:

6116

Middle Eastern (MID)

AF:

0.304

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.428

AC:

22657

AN:

52996

Other (OTH)

AF:

0.274

AC:

421

AN:

1539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

879

1758

2638

3517

4396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.379

Hom.:

30626

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

(source)

DANN

Benign

0.86

PhyloP100

-0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over