Variant 1-148483197-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001123068.3(PPIAL4G):c.56G>A(p.Arg19His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

PPIAL4G
NM_001123068.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.21

Variant links:

Genes affected

PPIAL4G (HGNC:33996): (peptidylprolyl isomerase A like 4G) Predicted to enable cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding and protein peptidyl-prolyl isomerization. Predicted to be active in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

PPIAL4G links:

LINC01138 (HGNC:49454): (long intergenic non-protein coding RNA 1138)

LINC01138 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09453827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIAL4G	NM_001123068.3 linkuse as main transcript	c.56G>A	p.Arg19His	missense_variant	1/1	ENST00000419275.3	NP_001116540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIAL4G	ENST00000419275.3 linkuse as main transcript	c.56G>A	p.Arg19His	missense_variant	1/1		NM_001123068.3	ENSP00000393845	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

250214

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

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

Mar 14, 2023

The c.56G>A (p.R19H) alteration is located in exon 1 (coding exon 1) of the PPIAL4G gene. This alteration results from a G to A substitution at nucleotide position 56, causing the arginine (R) at amino acid position 19 to be replaced by a histidine (H). 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

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.19

DANN

Benign

0.86

DEOGEN2

Benign

0.054

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.73

M_CAP

Benign

0.00088

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.050

Sift

Benign

0.25

Sift4G

Benign

0.27

Vest4

0.060

MVP

0.043

ClinPred

0.36

GERP RS

0.11

Varity_R

0.023

gMVP

0.49

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