5-139363853-T-G

Variant summary

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

The NM_016480.5(PAIP2):c.69T>G(p.His23Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: PAIP2 NM_016480.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.345

Genes affected

PAIP2 (HGNC:17970): (poly(A) binding protein interacting protein 2) Enables translation repressor activity. Involved in negative regulation of translational initiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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	UniProt
PAIP2	NM_016480.5	c.69T>G	p.His23Gln	missense_variant	2/4	ENST00000265192.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAIP2	ENST00000265192.9	c.69T>G	p.His23Gln	missense_variant	2/4	1	NM_016480.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461546 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.69T>G (p.H23Q) alteration is located in exon 2 (coding exon 1) of the PAIP2 gene. This alteration results from a T to G substitution at nucleotide position 69, causing the histidine (H) at amino acid position 23 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	0.0044	T
BayesDel_noAF	Benign	-0.23
Cadd	Uncertain	23
Dann	Benign	0.90
DEOGEN2	Benign	0.020	T;T;T;T;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T;.;T;.;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.55	N;N;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N;N;D;N;N
REVEL	Benign	0.28
Sift	Benign	0.37	T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T
Polyphen		0.028	.;B;.;B;B
Vest4		0.20, 0.20
MutPred		0.21		Loss of catalytic residue at H23 (P = 0.0354);Loss of catalytic residue at H23 (P = 0.0354);Loss of catalytic residue at H23 (P = 0.0354);Loss of catalytic residue at H23 (P = 0.0354);Loss of catalytic residue at H23 (P = 0.0354);
MVP		0.27
MPC		1.2
ClinPred		0.59	D
GERP RS		3.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.10
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: -5

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-138699542;