Genetic Variant PNMA5:p.Gly313Gly (chrX-152990660-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001184924.2(PNMA5):c.939G>T(p.Gly313Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00039 in 1,177,790 control chromosomes in the GnomAD database, including 4 homozygotes. There are 247 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 10 hem., cov: 24)

Exomes 𝑓: 0.00040 ( 4 hom. 237 hem. )

Consequence

PNMA5
NM_001184924.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.51

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant X-152990660-C-A is Benign according to our data. Variant chrX-152990660-C-A is described in ClinVar as [Benign]. Clinvar id is 756325.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNMA5	NM_001184924.2 link	c.939G>T	p.Gly313Gly	synonymous_variant	Exon 4 of 4	ENST00000535214.6	NP_001171853.1	Q96PV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PNMA5	ENST00000535214.6 link	c.939G>T	p.Gly313Gly	synonymous_variant	Exon 4 of 4	3	NM_001184924.2	ENSP00000445775.1	Q96PV4
PNMA5	ENST00000361887.5 link	c.939G>T	p.Gly313Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000354834.5	Q96PV4
PNMA5	ENST00000439251.3 link	c.939G>T	p.Gly313Gly	synonymous_variant	Exon 2 of 2	1		ENSP00000388850.1	Q96PV4
PNMA5	ENST00000452693.5 link	c.939G>T	p.Gly313Gly	synonymous_variant	Exon 3 of 3	2		ENSP00000392342.1	Q96PV4

Frequencies

GnomAD3 genomes

AF:

0.000249

AC:

AN:

112386

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34560

show subpopulations

Gnomad AFR

AF:

0.000421

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00511

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000792

AC:

118

AN:

149029

Hom.:

AF XY:

0.00122

AC XY:

AN XY:

47533

show subpopulations

Gnomad AFR exome

AF:

0.000159

Gnomad AMR exome

AF:

0.0000963

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00960

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000144

Gnomad OTH exome

AF:

0.000567

GnomAD4 exome

AF:

0.000405

AC:

431

AN:

1065351

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

237

AN XY:

345313

show subpopulations

Gnomad4 AFR exome

AF:

0.000202

Gnomad4 AMR exome

AF:

0.0000709

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00836

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.000426

GnomAD4 genome

AF:

0.000249

AC:

AN:

112439

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34623

show subpopulations

Gnomad4 AFR

AF:

0.000420

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00513

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000102

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.5

DANN

Benign

0.88

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over