Variant 9-69759913-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099666.2(PTAR1):c.26C>T(p.Ala9Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,522,822 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 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

PTAR1
NM_001099666.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

PTAR1 (HGNC:30449): (protein prenyltransferase alpha subunit repeat containing 1) Predicted to enable protein prenyltransferase activity. Predicted to be involved in protein prenylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PTAR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07172206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTAR1	NM_001099666.2 linkuse as main transcript	c.26C>T	p.Ala9Val	missense_variant	1/8	ENST00000340434.5	NP_001093136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
PTAR1	ENST00000340434.5 linkuse as main transcript	c.26C>T	p.Ala9Val	missense_variant	1/8	1	NM_001099666.2	ENSP00000344299	P1
PTAR1	ENST00000377200.9 linkuse as main transcript	c.26C>T	p.Ala9Val	missense_variant	1/5	1		ENSP00000366405
PTAR1	ENST00000472967.2 linkuse as main transcript	c.26C>T	p.Ala9Val	missense_variant	1/2	2		ENSP00000440164
PTAR1	ENST00000474925.2 linkuse as main transcript	n.43C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

137178

Hom.:

AF XY:

0.0000528

AC XY:

AN XY:

75700

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000992

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1371092

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

677950

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:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151730

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74108

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000611

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3458

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

May 09, 2023

The c.26C>T (p.A9V) alteration is located in exon 1 (coding exon 1) of the PTAR1 gene. This alteration results from a C to T substitution at nucleotide position 26, causing the alanine (A) at amino acid position 9 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

0.62

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

.;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.072

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.55

N;N;D

REVEL

Benign

0.074

Sift

Benign

0.27

T;D;D

Sift4G

Benign

0.063

T;T;T

Polyphen

0.58

.;P;.

Vest4

0.29

MutPred

0.37

Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);

MVP

0.043

MPC

0.38

ClinPred

0.15

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.24

gMVP

0.46

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