10-16484500-C-T

Position:

• chr10-16484500-C-T

Variant summary

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

The NM_001261836.2(PTER):​c.116C>T​(p.Pro39Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PTER NM_001261836.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

Genes affected

PTER (HGNC:9590): (phosphotriesterase related) Predicted to enable hydrolase activity, acting on ester bonds and zinc ion binding activity. Involved in epithelial cell differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTER	NM_001261836.2	c.116C>T	p.Pro39Leu	missense_variant	2/5	ENST00000535784.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTER	ENST00000535784.7	c.116C>T	p.Pro39Leu	missense_variant	2/5	1	NM_001261836.2	P1
PTER	ENST00000378000.5	c.116C>T	p.Pro39Leu	missense_variant	3/6	1		P1
PTER	ENST00000298942.4	c.116C>T	p.Pro39Leu	missense_variant	1/3	5
PTER	ENST00000423462.6	c.-15-1852C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74280

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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 30, 2023

The c.116C>T (p.P39L) alteration is located in exon 3 (coding exon 1) of the PTER gene. This alteration results from a C to T substitution at nucleotide position 116, causing the proline (P) at amino acid position 39 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	Benign	0.079
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;.
Eigen	Benign	-0.0028
Eigen_PC	Benign	-0.0040
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.2	M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.3	D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.20	B;B;B
Vest4		0.60
MutPred		0.53		Loss of glycosylation at P39 (P = 0.0127);Loss of glycosylation at P39 (P = 0.0127);Loss of glycosylation at P39 (P = 0.0127);
MVP		0.74
MPC		0.14
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.19
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1835606264; hg19: chr10-16526499;