6-149505643-T-C

Variant names:

• chr6-149505643-T-C
• rs1776759463
• NM_139126.4:c.1289A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_139126.4(PPIL4):​c.1289A>G​(p.Gln430Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 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. Q430L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPIL4 NM_139126.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037165046).

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.1289A>G	p.Gln430Arg	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.1289A>G	p.Gln430Arg	missense	Exon 13 of 13	ENSP00000253329.2	Q8WUA2
	PPIL4	ENST00000340881.2	TSL:1	c.187A>G	p.Lys63Glu	missense	Exon 3 of 3	ENSP00000344128.2	Q5T4S2
	PPIL4	ENST00000876132.1		c.932A>G	p.Gln311Arg	missense	Exon 10 of 10	ENSP00000546191.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60392

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	Benign	0.077
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.96
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.13	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.41
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.081
Vest4		0.093
MutPred		0.22		Loss of MoRF binding (P = 0.0268)
MVP		0.088
ClinPred		0.054	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
Mutation Taster		=97/3	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: rs1776759463; hg19: chr6-149826779;