5-139368787-G-T

Variant names:

• chr5-139368787-G-T
• rs1357183244
• NM_016480.5:c.373G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016480.5(PAIP2):​c.373G>T​(p.Gly125*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PAIP2 NM_016480.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 0 publications found

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]

SLC23A1 (HGNC:10974): (solute carrier family 23 member 1) The absorption of vitamin C into the body and its distribution to organs requires two sodium-dependent vitamin C transporters. This gene encodes one of the two transporters. The encoded protein is active in bulk vitamin C transport involving epithelial surfaces. Previously, this gene had an official symbol of SLC23A2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ENSG00000272742 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016480.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAIP2	NM_016480.5	MANE Select	c.373G>T	p.Gly125*	stop_gained	Exon 4 of 4	NP_057564.3
	SLC23A1	NM_005847.5	MANE Select	c.*20-1156C>A		intron	N/A	NP_005838.3
	PAIP2	NM_001033112.3		c.373G>T	p.Gly125*	stop_gained	Exon 4 of 4	NP_001028284.1	Q9BPZ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAIP2	ENST00000265192.9	TSL:1 MANE Select	c.373G>T	p.Gly125*	stop_gained	Exon 4 of 4	ENSP00000265192.4	Q9BPZ3
	PAIP2	ENST00000394795.6	TSL:1	c.373G>T	p.Gly125*	stop_gained	Exon 4 of 4	ENSP00000378275.2	Q9BPZ3
	PAIP2	ENST00000510080.1	TSL:1	c.373G>T	p.Gly125*	stop_gained	Exon 4 of 4	ENSP00000422508.1	Q9BPZ3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459482 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726250

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109934

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Benign	0.069	N
PhyloP100		2.5
Vest4		0.68
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=98/102	disease causing

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

Other links and lift over

dbSNP: rs1357183244; hg19: chr5-138704476;