Variant 8-26507674-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007257.6(PNMA2):c.1082A>G(p.Glu361Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,402,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PNMA2
NM_007257.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.21

Variant links:

Genes affected

PNMA2 (HGNC:9159): (PNMA family member 2) Predicted to be involved in positive regulation of apoptotic process. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

PNMA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05304402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNMA2	NM_007257.6 linkuse as main transcript	c.1082A>G	p.Glu361Gly	missense_variant	3/3	ENST00000522362.7	NP_009188.1	Q9UL42Q5U5Z3
PNMA2	XM_011544365.4 linkuse as main transcript	c.1082A>G	p.Glu361Gly	missense_variant	3/3		XP_011542667.1	Q9UL42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNMA2	ENST00000522362.7 linkuse as main transcript	c.1082A>G	p.Glu361Gly	missense_variant	3/3	1	NM_007257.6	ENSP00000429344.1		Q9UL42

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000997

AC:

AN:

200526

Hom.:

AF XY:

0.00000941

AC XY:

AN XY:

106254

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1402854

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691668

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000269

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

The c.1082A>G (p.E361G) alteration is located in exon 3 (coding exon 1) of the PNMA2 gene. This alteration results from a A to G substitution at nucleotide position 1082, causing the glutamic acid (E) at amino acid position 361 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

DANN

Benign

0.96

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.32

M_CAP

Benign

0.0031

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.54

REVEL

Benign

0.037

Sift

Benign

0.37

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.072

MutPred

0.18

Loss of solvent accessibility (P = 0.0387);

MVP

0.17

MPC

0.34

ClinPred

0.029

GERP RS

-1.3

Varity_R

0.031

gMVP

0.28

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