2-169606081-A-T

Variant names:

• chr2-169606081-A-T
• NM_004792.3:c.179A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004792.3(PPIG):​c.179A>T​(p.Tyr60Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPIG NM_004792.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.22

Genes affected

PPIG (HGNC:14650): (peptidylprolyl isomerase G) Enables cyclosporin A binding activity and peptidyl-prolyl cis-trans isomerase activity. Involved in protein peptidyl-prolyl isomerization. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIG	NM_004792.3	c.179A>T	p.Tyr60Phe	missense_variant	Exon 5 of 14	ENST00000260970.8	NP_004783.2
PPIG	XM_005246966.3	c.179A>T	p.Tyr60Phe	missense_variant	Exon 5 of 14		XP_005247023.1
PPIG	XM_005246967.2	c.179A>T	p.Tyr60Phe	missense_variant	Exon 5 of 14		XP_005247024.1
PPIG	XM_017005302.3	c.179A>T	p.Tyr60Phe	missense_variant	Exon 5 of 12		XP_016860791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIG	ENST00000260970.8	c.179A>T	p.Tyr60Phe	missense_variant	Exon 5 of 14	1	NM_004792.3	ENSP00000260970.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461196 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726914

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	27
DANN	Benign	0.89
DEOGEN2	Benign	0.27	T;T;T;.;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	.;D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.7	L;.;.;L;L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.5	D;D;D;D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.094	T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;T;D;T;D;T
Polyphen		0.99	D;B;B;D;D;.
Vest4		0.62
MutPred		0.90		Gain of disorder (P = 0.0711);.;Gain of disorder (P = 0.0711);Gain of disorder (P = 0.0711);Gain of disorder (P = 0.0711);Gain of disorder (P = 0.0711);
MVP		0.37
MPC		1.9
ClinPred		0.94	D
GERP RS		3.1
Varity_R		0.52
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-170462591;