Genetic Variant NM_013364.6:c.1150C>T (chrX-153058205-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013364.6(PNMA3):c.1150C>T(p.Arg384Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000306 in 1,210,520 control chromosomes in the GnomAD database, including 1 homozygotes. There are 100 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 6 hem., cov: 24)

Exomes 𝑓: 0.00031 ( 1 hom. 94 hem. )

Consequence

PNMA3
NM_013364.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05381301).

BS2

High Hemizygotes in GnomAd4 at 6 gene

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.1150C>T	p.Arg384Trp	missense	Exon 2 of 2	NP_037496.4	Q9UL41-1
	PNMA3	NM_001282535.2		c.1150C>T	p.Arg384Trp	missense	Exon 2 of 3	NP_001269464.1	Q9UL41-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNMA3	ENST00000593810.3	TSL:6 MANE Select	c.1150C>T	p.Arg384Trp	missense	Exon 2 of 2	ENSP00000469445.1	Q9UL41-1
PNMA3	ENST00000619635.1	TSL:1	c.1150C>T	p.Arg384Trp	missense	Exon 2 of 3	ENSP00000480719.1	Q9UL41-2
PNMA3	ENST00000424805.1	TSL:5	n.1150C>T		non_coding_transcript_exon	Exon 2 of 3	ENSP00000390576.1	Q9UL41-1

Frequencies

GnomAD3 genomes

AF:

0.000239

AC:

AN:

112798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000279

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000413

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000182

AC:

AN:

181515

AF XY:

0.000165

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000272

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000313

AC:

344

AN:

1097722

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

AN XY:

363122

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26398

American (AMR)

AF:

0.000227

AC:

AN:

35187

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19351

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.000130

AC:

AN:

54050

European-Finnish (FIN)

AF:

0.0000495

AC:

AN:

40433

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.000374

AC:

315

AN:

841900

Other (OTH)

AF:

0.000195

AC:

AN:

46070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000239

AC:

AN:

112798

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

AN XY:

34958

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31057

American (AMR)

AF:

0.000279

AC:

AN:

10759

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.000280

AC:

AN:

3575

South Asian (SAS)

AF:

0.00

AC:

AN:

2745

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6251

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000413

AC:

AN:

53299

Other (OTH)

AF:

0.00

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000289

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00134

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.022

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.72

M_CAP

Benign

0.0030

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PhyloP100

-1.1

PrimateAI

Uncertain

0.68

Sift4G

Uncertain

0.0030

Polyphen

0.0010

Vest4

0.11

MVP

0.35

ClinPred

0.019

GERP RS

-0.035

Varity_R

0.26

gMVP

0.39

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over