1-39745399-C-G

Variant names:

• chr1-39745399-C-G
• NM_006112.4:c.409C>G

Variant summary

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

The NM_006112.4(PPIE):​c.409C>G​(p.Arg137Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R137C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPIE NM_006112.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812

Genes affected

PPIE (HGNC:9258): (peptidylprolyl isomerase E) The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. This protein contains a highly conserved cyclophilin (CYP) domain as well as an RNA-binding domain. It was shown to possess PPIase and protein folding activities, and it also exhibits RNA-binding activity. Alternative splicing results in multiple transcript variants. A related pseudogene, which is also located on chromosome 1, has been identified. [provided by RefSeq, Aug 2010]

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=0.3215809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIE	NM_006112.4	c.409C>G	p.Arg137Gly	missense_variant	Exon 7 of 10	ENST00000324379.10	NP_006103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIE	ENST00000324379.10	c.409C>G	p.Arg137Gly	missense_variant	Exon 7 of 10	1	NM_006112.4	ENSP00000312769.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461870 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	.;T;.;.;T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.5	.;M;M;.;.;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;T;T;T;T;T
Sift4G	Uncertain	0.010	D;T;T;T;T;T
Polyphen		0.27, 0.28	.;B;B;.;.;.
Vest4		0.70, 0.70, 0.77, 0.62
MutPred		0.32		.;Loss of MoRF binding (P = 0.0114);Loss of MoRF binding (P = 0.0114);.;.;Loss of MoRF binding (P = 0.0114);
MVP		0.83
MPC		0.69
ClinPred		0.64	D
GERP RS		3.1
Varity_R		0.26
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40211071;