Genetic Variant PABIR3:p.Lys142Arg (chrX-134847462-A-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001388447.1(PABIR3):c.425A>G(p.Lys142Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 1,193,273 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000042 ( 0 hom. 26 hem. )

Consequence

PABIR3
NM_001388447.1 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -0.165

Publications

0 publications found

Variant links:

Genes affected

PABIR3 (HGNC:25202): (PABIR family member 3) Predicted to enable protein serine/threonine phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

PABIR3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009921104).

BP6

Variant X-134847462-A-G is Benign according to our data. Variant chrX-134847462-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1328276.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAdExome4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR3	NM_001388447.1 link	c.425A>G	p.Lys142Arg	missense_variant	Exon 7 of 11	ENST00000645433.2	NP_001375376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR3	ENST00000645433.2 link	c.425A>G	p.Lys142Arg	missense_variant	Exon 7 of 11		NM_001388447.1	ENSP00000496338.1		A0A2R8Y7S4

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112307

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000735

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000497

AC:

AN:

181062

AF XY:

0.0000908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000416

AC:

AN:

1080912

Hom.:

Cov.:

AF XY:

0.0000749

AC XY:

AN XY:

347074

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26119

American (AMR)

AF:

0.00

AC:

AN:

35072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19222

East Asian (EAS)

AF:

0.00

AC:

AN:

30085

South Asian (SAS)

AF:

0.000690

AC:

AN:

53623

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39956

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4080

European-Non Finnish (NFE)

AF:

0.00000846

AC:

AN:

827249

Other (OTH)

AF:

0.00

AC:

AN:

45506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112361

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34521

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31011

American (AMR)

AF:

0.00

AC:

AN:

10553

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.000369

AC:

AN:

2712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6131

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53295

Other (OTH)

AF:

0.00

AC:

AN:

1530

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0080

(source)

DANN

Benign

0.15

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.35

T;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0099

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.17

PROVEAN

Benign

1.1

.;N;.

REVEL

Benign

0.018

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

.;T;.

Polyphen

0.0

.;B;.

Vest4

0.023

MutPred

0.35

Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);

MVP

0.27

ClinPred

0.0086

GERP RS

-4.6

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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X-134847462-A-G

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