rs376513014

Variant names:

• chr22-21681382-G-A
• rs376513014
• NM_014337.4:c.379G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-21681382-G-A
• chr22-21681382-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014337.4(PPIL2):​c.379G>A​(p.Ala127Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000168 in 1,612,738 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: PPIL2 NM_014337.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.097771525).

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.379G>A	p.Ala127Thr	missense	Exon 7 of 20	NP_055152.1	Q13356-1
	PPIL2	NM_148176.3		c.379G>A	p.Ala127Thr	missense	Exon 7 of 21	NP_680481.1	Q13356-2
	PPIL2	NM_001317996.2		c.379G>A	p.Ala127Thr	missense	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.379G>A	p.Ala127Thr	missense	Exon 7 of 20	ENSP00000381812.3	Q13356-1
	PPIL2	ENST00000626352.2	TSL:1	c.379G>A	p.Ala127Thr	missense	Exon 7 of 21	ENSP00000486725.1	Q13356-2
	PPIL2	ENST00000335025.12	TSL:1	c.379G>A	p.Ala127Thr	missense	Exon 7 of 21	ENSP00000334553.7	Q13356-1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000756 AC: 19 AN: 251338 AF XY: 0.0000810

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000925

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000173 AC: 253 AN: 1460520 Hom.: 1 Cov.: 31 AF XY: 0.000150 AC XY: 109 AN XY: 726672

African (AFR) AF: 0.0000299 AC: 1 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86232

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000204 AC: 227 AN: 1110764

Other (OTH) AF: 0.000265 AC: 16 AN: 60370

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74360

African (AFR) AF: 0.0000724 AC: 3 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68046

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000149 Hom.: 0

Bravo AF: 0.000117

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.75	N
PhyloP100		4.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.072
Sift	Benign	0.48	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.49
MVP		0.26
ClinPred		0.20	T
GERP RS		0.50
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.027
gMVP		0.30
Mutation Taster		=83/17	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: rs376513014; hg19: chr22-22035671;