chr6-149505596-A-T

Variant names:

• chr6-149505596-A-T
• NM_139126.4:c.1336T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_139126.4(PPIL4):​c.1336T>A​(p.Ser446Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIL4 NM_139126.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72
• Publications: 0 publications found

Genes affected

PPIL4 (HGNC:15702): (peptidylprolyl isomerase like 4) This gene is a member of the cyclophilin family of peptidylprolyl isomerases. The cyclophilins are a highly conserved family, members of which play an important role in protein folding, immunosuppression by cyclosporin A, and infection of HIV-1 virions. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31428522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139126.4. 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
	PPIL4	NM_139126.4	MANE Select	c.1336T>A	p.Ser446Thr	missense	Exon 13 of 13	NP_624311.1	Q8WUA2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPIL4	ENST00000253329.3	TSL:1 MANE Select	c.1336T>A	p.Ser446Thr	missense	Exon 13 of 13	ENSP00000253329.2	Q8WUA2
	PPIL4	ENST00000340881.2	TSL:1	c.234T>A	p.Asp78Glu	missense	Exon 3 of 3	ENSP00000344128.2	Q5T4S2
	PPIL4	ENST00000876132.1		c.979T>A	p.Ser327Thr	missense	Exon 10 of 10	ENSP00000546191.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.11
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.96
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.7
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.20
Vest4		0.35
MutPred		0.099		Gain of disorder (P = 0.0529)
MVP		0.55
ClinPred		0.73	D
GERP RS		6.0
Varity_R		0.13
Mutation Taster		=74/26	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

hg19: chr6-149826732;