Variant chr10-16505025-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001261836.2(PTER):c.704T>C(p.Ile235Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PTER
NM_001261836.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.32

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:

PTER (HGNC:):

PTER links:

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ACMG classification

Classification made for transcript

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, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTER	NM_001261836.2 linkuse as main transcript	c.704T>C	p.Ile235Thr	missense_variant	4/5	ENST00000535784.7	NP_001248765.1	Q96BW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTER	ENST00000535784.7 linkuse as main transcript	c.704T>C	p.Ile235Thr	missense_variant	4/5	1	NM_001261836.2	ENSP00000439485.1	Q96BW5-1
PTER	ENST00000378000.5 linkuse as main transcript	c.704T>C	p.Ile235Thr	missense_variant	5/6	1		ENSP00000367239.1	Q96BW5-1
PTER	ENST00000423462.6 linkuse as main transcript	c.257T>C	p.Ile86Thr	missense_variant	3/4	3		ENSP00000389535.3	A0A0A0MSI3
PTER	ENST00000298942.4 linkuse as main transcript	c.699-6021T>C		intron_variant		5		ENSP00000298942.4	Q96BW5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727116

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 20, 2023

The c.704T>C (p.I235T) alteration is located in exon 5 (coding exon 3) of the PTER gene. This alteration results from a T to C substitution at nucleotide position 704, causing the isoleucine (I) at amino acid position 235 to be replaced by a threonine (T). 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

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;T;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

.;D;D

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Benign

-0.72

MutationAssessor

Pathogenic

3.0

M;.;M

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.7

D;.;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0030

D;.;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.93

P;.;P

Vest4

0.67

MutPred

0.43

Gain of disorder (P = 0.0091);.;Gain of disorder (P = 0.0091);

MVP

0.68

MPC

0.17

ClinPred

0.99

GERP RS

5.1

Varity_R

0.50

gMVP

0.75

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over