rs756245364

Variant names:

• chr15-64156048-T-C
• rs756245364
• NM_000942.5:c.626A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1 BP4_Moderate

The NM_000942.5(PPIB):​c.626A>G​(p.Lys209Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PPIB NM_000942.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84
• Publications: 2 publications found

Genes affected

PPIB (HGNC:9255): (peptidylprolyl isomerase B) The protein encoded by this gene is a cyclosporine-binding protein and is mainly located within the endoplasmic reticulum. It is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression. Variants have been identified in this protein that give rise to recessive forms of osteogenesis imperfecta. [provided by RefSeq, Oct 2009]

SNX22 (HGNC:16315): (sorting nexin 22) The protein encoded by this gene is a sorting nexin that is found in the cytoplasm, where it interacts with membrane-bound phosphatidylinositol 3-phosphate. The encoded protein may play a role in intracellular trafficking. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM1: In a modified_residue N6-succinyllysine; alternate (size 0) in uniprot entity PPIB_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.19601849).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000942.5. 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
	PPIB	NM_000942.5	MANE Select	c.626A>G	p.Lys209Arg	missense	Exon 5 of 5	NP_000933.1	P23284
	SNX22	NM_024798.3	MANE Select	c.*1540T>C		3_prime_UTR	Exon 7 of 7	NP_079074.2	Q96L94-1
	SNX22	NR_073534.2		n.2214T>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIB	ENST00000300026.4	TSL:1 MANE Select	c.626A>G	p.Lys209Arg	missense	Exon 5 of 5	ENSP00000300026.4	P23284
	SNX22	ENST00000325881.9	TSL:1 MANE Select	c.*1540T>C		3_prime_UTR	Exon 7 of 7	ENSP00000323435.4	Q96L94-1
	SNX22	ENST00000560997.1	TSL:1	n.1935T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249608 AF XY: 0.0000222

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: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461890 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.13
Sift	Benign	0.12	T
Sift4G	Benign	0.065	T
Polyphen		0.16	B
Vest4		0.36
MutPred		0.34		Gain of sheet (P = 0.0101)
MVP		0.62
MPC		0.38
ClinPred		0.31	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.40
Mutation Taster		=49/51	disease causing

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: rs756245364; hg19: chr15-64448247;