6-109427147-C-A

Position:

• chr6-109427147-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173672.5(PPIL6):​c.430G>T​(p.Val144Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPIL6 NM_173672.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07

Genes affected

PPIL6 (HGNC:21557): (peptidylprolyl isomerase like 6) Predicted to enable peptidyl-prolyl cis-trans isomerase activity. Predicted to be involved in protein folding and protein peptidyl-prolyl isomerization. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PPIL6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIL6	NM_173672.5	c.430G>T	p.Val144Leu	missense_variant	4/8	ENST00000521072.7	NP_775943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIL6	ENST00000521072.7	c.430G>T	p.Val144Leu	missense_variant	4/8	1	NM_173672.5	ENSP00000427929.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.430G>T (p.V144L) alteration is located in exon 4 (coding exon 4) of the PPIL6 gene. This alteration results from a G to T substitution at nucleotide position 430, causing the valine (V) at amino acid position 144 to be replaced by a leucine (L). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.9	M;.;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.015	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;.
Polyphen		1.0	D;.;.;.
Vest4		0.72
MutPred		0.77		Loss of stability (P = 0.1774);.;Loss of stability (P = 0.1774);.;
MVP		0.48
MPC		0.16
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.47
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.25		Position offset: 9

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: chr6-109748350;