Variant 9-69759904-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001099666.2(PTAR1):c.35T>G(p.Val12Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000851 in 1,526,996 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)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

PTAR1
NM_001099666.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.30

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTAR1	NM_001099666.2 linkuse as main transcript	c.35T>G	p.Val12Gly	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.35T>G	p.Val12Gly	missense_variant	1/8	1	NM_001099666.2	ENSP00000344299	P1
PTAR1	ENST00000377200.9 linkuse as main transcript	c.35T>G	p.Val12Gly	missense_variant	1/5	1		ENSP00000366405
PTAR1	ENST00000472967.2 linkuse as main transcript	c.35T>G	p.Val12Gly	missense_variant	1/2	2		ENSP00000440164
PTAR1	ENST00000474925.2 linkuse as main transcript	n.52T>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD3 exomes

AF:

0.0000495

AC:

AN:

141556

Hom.:

AF XY:

0.0000128

AC XY:

AN XY:

78040

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000872

AC:

AN:

1375434

Hom.:

Cov.:

AF XY:

0.00000588

AC XY:

AN XY:

680280

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000324

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:

9.35e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151562

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73996

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

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

Bravo

AF:

0.0000227

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

Sep 29, 2022

The c.35T>G (p.V12G) alteration is located in exon 1 (coding exon 1) of the PTAR1 gene. This alteration results from a T to G substitution at nucleotide position 35, causing the valine (V) at amino acid position 12 to be replaced by a glycine (G). 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

0.74

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.024

.;T;.

Eigen

Benign

0.012

Eigen_PC

Benign

0.0072

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T

M_CAP

Pathogenic

0.72

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.1

N;N;D

REVEL

Benign

0.28

Sift

Uncertain

0.015

D;T;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.81

.;P;.

Vest4

0.62

MutPred

0.35

Loss of stability (P = 0.0079);Loss of stability (P = 0.0079);Loss of stability (P = 0.0079);

MVP

0.082

MPC

0.70

ClinPred

0.41

GERP RS

2.9

Varity_R

0.69

gMVP

0.81

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