1-148483024-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001123068.3(PPIAL4G):ā€‹c.229T>Cā€‹(p.Ser77Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000781 in 1,612,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 28)
Exomes š‘“: 0.000081 ( 0 hom. )

Consequence

PPIAL4G
NM_001123068.3 missense

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.56
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]
LINC01138 (HGNC:49454): (long intergenic non-protein coding RNA 1138)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.29124027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPIAL4GNM_001123068.3 linkuse as main transcriptc.229T>C p.Ser77Pro missense_variant 1/1 ENST00000419275.3 NP_001116540.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPIAL4GENST00000419275.3 linkuse as main transcriptc.229T>C p.Ser77Pro missense_variant 1/1 NM_001123068.3 ENSP00000393845 P1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152096
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000926
AC:
23
AN:
248300
Hom.:
0
AF XY:
0.0000740
AC XY:
10
AN XY:
135096
show subpopulations
Gnomad AFR exome
AF:
0.0000673
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000116
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000808
AC:
118
AN:
1460790
Hom.:
0
Cov.:
31
AF XY:
0.0000867
AC XY:
63
AN XY:
726714
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000201
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:
0.0000908
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152096
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.0000642

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 submitterclinical testingAmbry GeneticsAug 09, 2021The c.229T>C (p.S77P) alteration is located in exon 1 (coding exon 1) of the PPIAL4G gene. This alteration results from a T to C substitution at nucleotide position 229, causing the serine (S) at amino acid position 77 to be replaced by a proline (P). 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
0.19
BayesDel_addAF
Benign
-0.029
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
17
DANN
Benign
0.95
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.47
N
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.0011
T
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.98
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Pathogenic
-4.8
D
Sift
Uncertain
0.0090
D
Sift4G
Uncertain
0.0050
D
Vest4
0.49
MVP
0.043
ClinPred
0.99
D
GERP RS
0.11
Varity_R
0.71
gMVP
0.72

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.

Other links and lift over

dbSNP: rs1181336776; hg19: chr1-147955116; API