Variant chr2-71202481-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020459.1(PAIP2B):c.109A>T(p.Met37Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PAIP2B
NM_020459.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

PAIP2B (HGNC:29200): (poly(A) binding protein interacting protein 2B) Most mRNAs, except for histones, contain a 3-prime poly(A) tail. Poly(A)-binding protein (PABP; see MIM 604679) enhances translation by circularizing mRNA through its interaction with the translation initiation factor EIF4G1 (MIM 600495) and the poly(A) tail. Various PABP-binding proteins regulate PABP activity, including PAIP1 (MIM 605184), a translational stimulator, and PAIP2A (MIM 605604) and PAIP2B, translational inhibitors (Derry et al., 2006 [PubMed 17381337]).[supplied by OMIM, Mar 2008]

PAIP2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAIP2B	NM_020459.1 linkuse as main transcript	c.109A>T	p.Met37Leu	missense_variant	2/4	ENST00000244221.9	NP_065192.1	Q9ULR5
PAIP2B	XM_011532842.4 linkuse as main transcript	c.172A>T	p.Met58Leu	missense_variant	2/4		XP_011531144.1
PAIP2B	XM_005264310.5 linkuse as main transcript	c.109A>T	p.Met37Leu	missense_variant	3/5		XP_005264367.1	Q9ULR5
PAIP2B	XM_005264311.5 linkuse as main transcript	c.109A>T	p.Met37Leu	missense_variant	2/4		XP_005264368.1	Q9ULR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAIP2B	ENST00000244221.9 linkuse as main transcript	c.109A>T	p.Met37Leu	missense_variant	2/4	1	NM_020459.1	ENSP00000244221.8		Q9ULR5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461528

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727072

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 01, 2024

The c.109A>T (p.M37L) alteration is located in exon 2 (coding exon 1) of the PAIP2B gene. This alteration results from a A to T substitution at nucleotide position 109, causing the methionine (M) at amino acid position 37 to be replaced by a leucine (L). 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

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.54

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.74

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.29

Sift

Uncertain

0.0050

Sift4G

Pathogenic

0.0

Polyphen

0.85

Vest4

0.72

MutPred

0.41

Loss of phosphorylation at Y34 (P = 0.1618);

MVP

0.33

MPC

0.24

ClinPred

0.96

GERP RS

5.4

Varity_R

0.60

gMVP

0.65

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over