Genetic Variant PABIR2:p.Ala212Ala (chrX-134781844-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001387468.1(PABIR2):c.636G>A(p.Ala212Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,197,863 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 81 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00025 ( 0 hom. 75 hem. )

Consequence

PABIR2
NM_001387468.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.940

Publications

1 publications found

Variant links:

Genes affected

PABIR2 (HGNC:30490): (PABIR family member 2) Predicted to enable protein serine/threonine phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. Predicted to be part of collagen trimer. [provided by Alliance of Genome Resources, Apr 2022]

PABIR2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant X-134781844-C-T is Benign according to our data. Variant chrX-134781844-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661478.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.94 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1 link	c.636G>A	p.Ala212Ala	synonymous_variant	Exon 9 of 10	ENST00000343004.10	NP_001374397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR2	ENST00000343004.10 link	c.636G>A	p.Ala212Ala	synonymous_variant	Exon 9 of 10	1	NM_001387468.1	ENSP00000339207.6		G1UD79

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

111269

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000482

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:

0.000226

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000146

AC:

AN:

177855

AF XY:

0.0000957

show subpopulations

Gnomad AFR exome

AF:

0.0000774

Gnomad AMR exome

AF:

0.000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000249

AC:

271

AN:

1086594

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

AN XY:

354290

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26246

American (AMR)

AF:

0.000259

AC:

AN:

34796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19122

East Asian (EAS)

AF:

0.0000333

AC:

AN:

30038

South Asian (SAS)

AF:

0.0000192

AC:

AN:

52208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4084

European-Non Finnish (NFE)

AF:

0.000286

AC:

239

AN:

835008

Other (OTH)

AF:

0.000395

AC:

AN:

45614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000171

AC:

AN:

111269

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

33477

show subpopulations

African (AFR)

AF:

0.0000653

AC:

AN:

30631

American (AMR)

AF:

0.000482

AC:

AN:

10374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3591

South Asian (SAS)

AF:

0.00

AC:

AN:

2639

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000226

AC:

AN:

53058

Other (OTH)

AF:

0.00

AC:

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000193

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PABIR2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.086

(source)

DANN

Benign

0.30

PhyloP100

-0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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-134781844-C-T

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