Variant 10-16484796-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001261836.2(PTER):c.412A>T(p.Arg138Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00017 in 1,607,468 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

PTER
NM_001261836.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

Variant links:

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]

PTER links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3151706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTER	NM_001261836.2 linkuse as main transcript	c.412A>T	p.Arg138Trp	missense_variant	2/5	ENST00000535784.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTER	ENST00000535784.7 linkuse as main transcript	c.412A>T	p.Arg138Trp	missense_variant	2/5	1	NM_001261836.2	P1	Q96BW5-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000218

AC:

AN:

243678

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

131488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000486

Gnomad ASJ exome

AF:

0.000212

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000348

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000252

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000165

AC:

240

AN:

1455196

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

125

AN XY:

723536

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000394

Gnomad4 ASJ exome

AF:

0.000428

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000354

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000516

GnomAD4 genome

AF:

0.000223

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000570

Hom.:

Bravo

AF:

0.000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.412A>T (p.R138W) alteration is located in exon 3 (coding exon 1) of the PTER gene. This alteration results from a A to T substitution at nucleotide position 412, causing the arginine (R) at amino acid position 138 to be replaced by a tryptophan (W). 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

0.19

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

T;T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.027

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.9

M;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.024

D;D;D

Sift4G

Benign

0.096

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.54

MVP

0.88

MPC

0.18

ClinPred

0.40

GERP RS

1.3

Varity_R

0.18

gMVP

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over