dbSNP rs200312685: PTAR1:p.Met336Val (chr9-69718545-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099666.2(PTAR1):c.1006A>G(p.Met336Val) variant causes a missense change. The variant allele was found at a frequency of 0.000426 in 1,613,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

PTAR1
NM_001099666.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.98

Publications

4 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23929754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTAR1	NM_001099666.2 link	c.1006A>G	p.Met336Val	missense_variant	Exon 8 of 8	ENST00000340434.5	NP_001093136.1	Q7Z6K3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PTAR1	ENST00000340434.5 link	c.1006A>G	p.Met336Val	missense_variant	Exon 8 of 8	1	NM_001099666.2	ENSP00000344299.4	Q7Z6K3
PTAR1	ENST00000377200.9 link	c.850A>G	p.Met284Val	missense_variant	Exon 5 of 5	1		ENSP00000366405.5	X6R9N0
PTAR1	ENST00000415701.6 link	c.301A>G	p.Met101Val	missense_variant	Exon 3 of 3	3		ENSP00000405943.2	J3KQP8

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000412

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000237

AC:

AN:

248862

AF XY:

0.000244

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000444

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000446

AC:

652

AN:

1461450

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

279

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33466

American (AMR)

AF:

0.000112

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000549

AC:

610

AN:

1111706

Other (OTH)

AF:

0.000563

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41438

American (AMR)

AF:

0.000131

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68020

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000215

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000838

AC:

ExAC

AF:

0.000223

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 21, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1006A>G (p.M336V) alteration is located in exon 8 (coding exon 8) of the PTAR1 gene. This alteration results from a A to G substitution at nucleotide position 1006, causing the methionine (M) at amino acid position 336 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

Benign

0.099

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.83

PhyloP100

7.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.19

Sift

Benign

0.030

D;T

Sift4G

Uncertain

0.018

D;T

Polyphen

0.98

.;D

Vest4

0.55

MVP

0.43

MPC

0.92

ClinPred

0.079

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.58

Mutation Taster

=62/38

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over