6-149505505-C-G

Variant names:

• chr6-149505505-C-G
• rs764028936
• NM_139126.4:c.1427G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139126.4(PPIL4):​c.1427G>C​(p.Arg476Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R476Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIL4 NM_139126.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17622492).

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.1427G>C	p.Arg476Pro	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.1427G>C	p.Arg476Pro	missense	Exon 13 of 13	ENSP00000253329.2	Q8WUA2
	PPIL4	ENST00000340881.2	TSL:1	c.325G>C	p.Glu109Gln	missense	Exon 3 of 3	ENSP00000344128.2	Q5T4S2
	PPIL4	ENST00000876132.1		c.1070G>C	p.Arg357Pro	missense	Exon 10 of 10	ENSP00000546191.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.91
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.076
Vest4		0.19
MutPred		0.14		Gain of MoRF binding (P = 0.0215)
MVP		0.51
ClinPred		0.81	D
GERP RS		4.3
Varity_R		0.26
Mutation Taster		=42/58	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: rs764028936; hg19: chr6-149826641;