6-109431314-G-A

Position:

• chr6-109431314-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173672.5(PPIL6):​c.263C>T​(p.Ser88Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPIL6 NM_173672.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34783274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPIL6	NM_173672.5	c.263C>T	p.Ser88Phe	missense_variant	3/8	ENST00000521072.7	NP_775943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPIL6	ENST00000521072.7	c.263C>T	p.Ser88Phe	missense_variant	3/8	1	NM_173672.5	ENSP00000427929.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.13e-7 AC: 1 AN: 1402912 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 695498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Jun 16, 2023

The c.263C>T (p.S88F) alteration is located in exon 3 (coding exon 3) of the PPIL6 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the serine (S) at amino acid position 88 to be replaced by a phenylalanine (F). 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	0.33
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.8	M;.;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.019	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;.
Polyphen		0.98	D;.;.;.
Vest4		0.55
MutPred		0.40		Loss of disorder (P = 0.0146);.;Loss of disorder (P = 0.0146);.;
MVP		0.52
MPC		0.16
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.28
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr6-109752517; COSMIC: COSV70022144; COSMIC: COSV70022144;