NM_014337.4:c.372C>T

Variant names:

• chr22-21681375-C-T
• rs35412833
• NM_014337.4:c.372C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_014337.4(PPIL2):​c.372C>T​(p.Asn124Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,613,556 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (27 hom.)
• Consequence: PPIL2 NM_014337.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.658
• Publications: 2 publications found

Genes affected

PPIL2 (HGNC:9261): (peptidylprolyl isomerase like 2) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved ubiquitous family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. This protein interacts with the proteinase inhibitor eglin c and is localized in the nucleus. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 22-21681375-C-T is Benign according to our data. Variant chr22-21681375-C-T is described in ClinVar as Benign. ClinVar VariationId is 769150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.658 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0101 (1542/152324) while in subpopulation AFR AF = 0.0352 (1465/41564). AF 95% confidence interval is 0.0337. There are 22 homozygotes in GnomAd4. There are 707 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014337.4. 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
	PPIL2	NM_014337.4	MANE Select	c.372C>T	p.Asn124Asn	synonymous	Exon 7 of 20	NP_055152.1	Q13356-1
	PPIL2	NM_148176.3		c.372C>T	p.Asn124Asn	synonymous	Exon 7 of 21	NP_680481.1	Q13356-2
	PPIL2	NM_001317996.2		c.372C>T	p.Asn124Asn	synonymous	Exon 7 of 21	NP_001304925.1	Q13356-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL2	ENST00000398831.8	TSL:1 MANE Select	c.372C>T	p.Asn124Asn	synonymous	Exon 7 of 20	ENSP00000381812.3	Q13356-1
	PPIL2	ENST00000626352.2	TSL:1	c.372C>T	p.Asn124Asn	synonymous	Exon 7 of 21	ENSP00000486725.1	Q13356-2
	PPIL2	ENST00000335025.12	TSL:1	c.372C>T	p.Asn124Asn	synonymous	Exon 7 of 21	ENSP00000334553.7	Q13356-1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1541 AN: 152206 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00285 AC: 716 AN: 251378 AF XY: 0.00205

Gnomad AFR exome AF: 0.0369

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00120 AC: 1758 AN: 1461232 Hom.: 27 Cov.: 31 AF XY: 0.00102 AC XY: 745 AN XY: 726998

African (AFR) AF: 0.0383 AC: 1282 AN: 33468

American (AMR) AF: 0.00215 AC: 96 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00291 AC: 76 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.000127 AC: 141 AN: 1111414

Other (OTH) AF: 0.00240 AC: 145 AN: 60384

GnomAD4 genome AF: 0.0101 AC: 1542 AN: 152324 Hom.: 22 Cov.: 32 AF XY: 0.00949 AC XY: 707 AN XY: 74484

African (AFR) AF: 0.0352 AC: 1465 AN: 41564

American (AMR) AF: 0.00268 AC: 41 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68034

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00493 Hom.: 9

Bravo AF: 0.0116

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	1.4
DANN	Benign	0.91
PhyloP100		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35412833; hg19: chr22-22035664;