6-149505666-T-G

Variant names:

• chr6-149505666-T-G
• NM_139126.4:c.1266A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139126.4(PPIL4):​c.1266A>C​(p.Glu422Asp) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIL4 NM_139126.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.927

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07092813).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPIL4	NM_139126.4	c.1266A>C	p.Glu422Asp	missense_variant	Exon 13 of 13	ENST00000253329.3	NP_624311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPIL4	ENST00000253329.3	c.1266A>C	p.Glu422Asp	missense_variant	Exon 13 of 13	1	NM_139126.4	ENSP00000253329.2
PPIL4	ENST00000340881.2	c.164A>C	p.Lys55Thr	missense_variant	Exon 3 of 3	1		ENSP00000344128.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1266A>C (p.E422D) alteration is located in exon 13 (coding exon 13) of the PPIL4 gene. This alteration results from a A to C substitution at nucleotide position 1266, causing the glutamic acid (E) at amino acid position 422 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	0.048
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.041
Sift	Benign	0.34	T
Sift4G	Benign	0.52	T
Polyphen		0.39	B
Vest4		0.10
MutPred		0.21		Loss of sheet (P = 7e-04);
MVP		0.16
MPC		0.27
ClinPred		0.40	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.066
gMVP		0.060

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-149826802;