1-148483185-T-C

Position:

• chr1-148483185-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001123068.3(PPIAL4G):​c.68A>G​(p.Lys23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,586 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 (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPIAL4G NM_001123068.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

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)

ACMG classification

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=0.11708897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIAL4G	NM_001123068.3	c.68A>G	p.Lys23Arg	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	c.68A>G	p.Lys23Arg	missense_variant	1/1		NM_001123068.3	ENSP00000393845	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461586 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 28

Bravo AF: 0.00000378

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

Mar 07, 2024

The c.68A>G (p.K23R) alteration is located in exon 1 (coding exon 1) of the PPIAL4G gene. This alteration results from a A to G substitution at nucleotide position 68, causing the lysine (K) at amino acid position 23 to be replaced by an arginine (R). 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	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.22	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.00062	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.88	N
Sift	Benign	0.038	D
Sift4G	Uncertain	0.032	D
Vest4		0.11
MVP		0.10
ClinPred		0.19	T
GERP RS		0.11
Varity_R		0.12
gMVP		0.34

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

Other links and lift over

dbSNP: rs1651933004; hg19: chr1-147955277;