dbSNP rs782127676: PNMA5:p.Val369Met (chrX-152990494-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_001184924.2(PNMA5):c.1105G>A(p.Val369Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000639 in 1,188,457 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V369L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000069 ( 0 hom. 23 hem. )

Consequence

PNMA5
NM_001184924.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.789

Publications

4 publications found

Variant links:

Genes affected

PNMA5 (HGNC:18743): (PNMA family member 5) This gene encodes a member of the paraneoplastic Ma antigen protein family. These proteins have been implicated in the development of paraneoplastic disorders resulting from an immune response directed against them. Paraneoplastic disorders are the result of an abnormal immune response to a tumor. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2011]

PNMA5 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=0.044269025).

BS2

High Hemizygotes in GnomAdExome4 at 23 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184924.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNMA5	NM_001184924.2	MANE Select	c.1105G>A	p.Val369Met	missense	Exon 4 of 4	NP_001171853.1	Q96PV4
PNMA5	NM_001103150.1		c.1105G>A	p.Val369Met	missense	Exon 2 of 2	NP_001096620.1	Q96PV4
PNMA5	NM_001103151.1		c.1105G>A	p.Val369Met	missense	Exon 3 of 3	NP_001096621.1	Q96PV4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNMA5	ENST00000535214.6	TSL:3 MANE Select	c.1105G>A	p.Val369Met	missense	Exon 4 of 4	ENSP00000445775.1	Q96PV4
PNMA5	ENST00000361887.5	TSL:1	c.1105G>A	p.Val369Met	missense	Exon 2 of 2	ENSP00000354834.5	Q96PV4
PNMA5	ENST00000439251.3	TSL:1	c.1105G>A	p.Val369Met	missense	Exon 2 of 2	ENSP00000388850.1	Q96PV4

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000254

AC:

AN:

157585

AF XY:

0.0000201

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000438

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000688

AC:

AN:

1075859

Hom.:

Cov.:

AF XY:

0.0000658

AC XY:

AN XY:

349623

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25479

American (AMR)

AF:

0.00

AC:

AN:

31012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17726

East Asian (EAS)

AF:

0.00

AC:

AN:

30054

South Asian (SAS)

AF:

0.0000602

AC:

AN:

49822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39823

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4008

European-Non Finnish (NFE)

AF:

0.0000828

AC:

AN:

832849

Other (OTH)

AF:

0.0000444

AC:

AN:

45086

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

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:

0.0000178

AC:

AN:

112598

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34746

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30983

American (AMR)

AF:

0.00

AC:

AN:

10722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2657

East Asian (EAS)

AF:

0.00

AC:

AN:

3580

South Asian (SAS)

AF:

0.00

AC:

AN:

2730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6221

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53259

Other (OTH)

AF:

0.00

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000434

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

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

0.10

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.18

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.020

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.37

M_CAP

Benign

0.0010

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

-0.79

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.21

REVEL

Benign

0.010

Sift

Benign

0.16

Sift4G

Benign

0.072

Polyphen

0.010

Vest4

0.017

MutPred

0.17

Gain of helix (P = 0.0425)

MVP

0.28

MPC

0.098

ClinPred

0.019

GERP RS

-6.6

Varity_R

0.033

gMVP

0.24

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

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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