5-139363864-A-T

Position:

• chr5-139363864-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016480.5(PAIP2):​c.80A>T​(p.Asp27Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,530 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: 6.8e-7 (0 hom.)
• Consequence: PAIP2 NM_016480.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34788412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAIP2	NM_016480.5	c.80A>T	p.Asp27Val	missense_variant	2/4	ENST00000265192.9	NP_057564.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAIP2	ENST00000265192.9	c.80A>T	p.Asp27Val	missense_variant	2/4	1	NM_016480.5	ENSP00000265192	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461530 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727092

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: 9.00e-7

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

Apr 07, 2022

The c.80A>T (p.D27V) alteration is located in exon 2 (coding exon 1) of the PAIP2 gene. This alteration results from a A to T substitution at nucleotide position 80, causing the aspartic acid (D) at amino acid position 27 to be replaced by a valine (V). 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	0.30
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;T;T;T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;.;D;.;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	.;L;.;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0080	D;D;D;D;D
Sift4G	Uncertain	0.025	D;D;D;D;D
Polyphen		0.33	.;B;.;B;B
Vest4		0.58, 0.62
MutPred		0.23		Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);Loss of disorder (P = 0.0402);
MVP		0.17
MPC		1.0
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.27
gMVP		0.85

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.

Other links and lift over

hg19: chr5-138699553;