Variant 1-148483059-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001123068.3(PPIAL4G):c.194G>C(p.Gly65Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPIAL4G
NM_001123068.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

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 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
PPIAL4G	NM_001123068.3 linkuse as main transcript	c.194G>C	p.Gly65Ala	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.194G>C	p.Gly65Ala	missense_variant	1/1		NM_001123068.3	ENSP00000393845	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248960

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135302

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000137

AC:

AN:

1461028

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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.:

Bravo

AF:

0.00000756

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

Feb 27, 2024

The c.194G>C (p.G65A) alteration is located in exon 1 (coding exon 1) of the PPIAL4G gene. This alteration results from a G to C substitution at nucleotide position 194, causing the glycine (G) at amino acid position 65 to be replaced by an alanine (A). 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

0.15

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.54

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

M_CAP

Benign

0.0026

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.91

MutationTaster

Benign

0.94

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.4

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Vest4

0.66

MVP

0.25

ClinPred

1.0

GERP RS

0.11

Varity_R

0.78

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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