1-148483111-A-G

Position:

• chr1-148483111-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001123068.3(PPIAL4G):​c.142T>C​(p.Tyr48His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPIAL4G NM_001123068.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34345764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIAL4G	NM_001123068.3	c.142T>C	p.Tyr48His	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.142T>C	p.Tyr48His	missense_variant	1/1		NM_001123068.3	ENSP00000393845	P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461202 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726910

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

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

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 17, 2023

The c.142T>C (p.Y48H) 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 142, causing the tyrosine (Y) at amino acid position 48 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	0.28
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.1	D
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Vest4		0.43
MVP		0.10
ClinPred		1.0	D
GERP RS		0.11
Varity_R		0.44
gMVP		0.66

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: rs1651929007; hg19: chr1-147955203;