10-16484773-A-T

Position:

• chr10-16484773-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000535784.7(PTER):​c.389A>T​(p.Asp130Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: PTER ENST00000535784.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTER	NM_001261836.2	c.389A>T	p.Asp130Val	missense_variant	2/5	ENST00000535784.7	NP_001248765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTER	ENST00000535784.7	c.389A>T	p.Asp130Val	missense_variant	2/5	1	NM_001261836.2	ENSP00000439485	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 26, 2024

The c.389A>T (p.D130V) 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 389, causing the aspartic acid (D) at amino acid position 130 to be replaced by a valine (V). 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	0.67
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;T;.
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.019
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.8	M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.28
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.067	T;T;T
Polyphen		0.15	B;B;B
Vest4		0.71
MutPred		0.76		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.68
MPC		0.12
ClinPred		0.97	D
GERP RS		3.2
Varity_R		0.52
gMVP		0.88

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.

Other links and lift over

hg19: chr10-16526772;