1-39753393-C-T

Variant names:

• chr1-39753393-C-T
• rs1046988
• NM_006112.4:c.*38C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006112.4(PPIE):​c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,602,936 control chromosomes in the GnomAD database, including 102,564 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7671 hom., cov: 33)
  • Exomes 𝑓: 0.36 (94893 hom.)
• Consequence: PPIE NM_006112.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006112.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIE	NM_006112.4	MANE Select	c.*38C>T		3_prime_UTR	Exon 10 of 10	NP_006103.1	Q9UNP9-1
	PPIE	NM_001195007.2		c.837+341C>T		intron	N/A	NP_001181936.1	Q9UNP9-3
	PPIE	NM_203456.3		c.837+341C>T		intron	N/A	NP_982281.1	Q9UNP9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIE	ENST00000324379.10	TSL:1 MANE Select	c.*38C>T		3_prime_UTR	Exon 10 of 10	ENSP00000312769.5	Q9UNP9-1
	PPIE	ENST00000372830.5	TSL:1	c.837+341C>T		intron	N/A	ENSP00000361918.1	Q9UNP9-3
	PPIE	ENST00000356511.6	TSL:1	c.837+341C>T		intron	N/A	ENSP00000348904.2	Q9UNP9-2

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46864 AN: 152060 Hom.: 7658 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.329 AC: 78916 AN: 239554 AF XY: 0.338

Gnomad AFR exome AF: 0.194

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.251

Gnomad FIN exome AF: 0.366

Gnomad NFE exome AF: 0.363

Gnomad OTH exome AF: 0.324

GnomAD4 exome AF: 0.358 AC: 519446 AN: 1450758 Hom.: 94893 Cov.: 37 AF XY: 0.359 AC XY: 258984 AN XY: 721118

African (AFR) AF: 0.184 AC: 6107 AN: 33196

American (AMR) AF: 0.242 AC: 10419 AN: 43108

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 9025 AN: 25240

East Asian (EAS) AF: 0.238 AC: 9431 AN: 39638

South Asian (SAS) AF: 0.393 AC: 33231 AN: 84522

European-Finnish (FIN) AF: 0.361 AC: 19116 AN: 52930

Middle Eastern (MID) AF: 0.265 AC: 1515 AN: 5718

European-Non Finnish (NFE) AF: 0.370 AC: 409876 AN: 1106552

Other (OTH) AF: 0.346 AC: 20726 AN: 59854

GnomAD4 genome AF: 0.308 AC: 46899 AN: 152178 Hom.: 7671 Cov.: 33 AF XY: 0.308 AC XY: 22927 AN XY: 74404

African (AFR) AF: 0.197 AC: 8202 AN: 41532

American (AMR) AF: 0.279 AC: 4266 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1265 AN: 5176

South Asian (SAS) AF: 0.406 AC: 1960 AN: 4828

European-Finnish (FIN) AF: 0.361 AC: 3818 AN: 10584

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25007 AN: 67986

Other (OTH) AF: 0.288 AC: 609 AN: 2112

Alfa AF: 0.342 Hom.: 16315

Bravo AF: 0.291

Asia WGS AF: 0.320 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1046988; hg19: chr1-40219065; COSMIC: COSV60971215; COSMIC: COSV60971215;