Genetic Variant PABIR2:p.Ala245Thr (chrX-134772210-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001387468.1(PABIR2):c.733G>A(p.Ala245Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,205,422 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000034 ( 0 hom. 9 hem. )

Consequence

PABIR2
NM_001387468.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.82

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01403904).

BP6

Variant X-134772210-C-T is Benign according to our data. Variant chrX-134772210-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3207806.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387468.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PABIR2	NM_001387468.1	MANE Select	c.733G>A	p.Ala245Thr	missense	Exon 10 of 10	NP_001374397.1	G1UD79
PABIR2	NM_001331088.1		c.745G>A	p.Ala249Thr	missense	Exon 10 of 10	NP_001318017.1
PABIR2	NM_001331089.1		c.742G>A	p.Ala248Thr	missense	Exon 10 of 10	NP_001318018.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PABIR2	ENST00000343004.10	TSL:1 MANE Select	c.733G>A	p.Ala245Thr	missense	Exon 10 of 10	ENSP00000339207.6	G1UD79
PABIR2	ENST00000370790.5	TSL:1	c.673G>A	p.Ala225Thr	missense	Exon 9 of 9	ENSP00000359826.1	Q7Z309-1
PABIR2	ENST00000896544.1		c.742G>A	p.Ala248Thr	missense	Exon 10 of 10	ENSP00000566603.1

Frequencies

GnomAD3 genomes

AF:

0.0000714

AC:

AN:

112030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000841

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.000665

GnomAD2 exomes

AF:

0.000106

AC:

AN:

179761

AF XY:

0.0000621

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00119

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1093341

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

359219

show subpopulations

African (AFR)

AF:

0.0000380

AC:

AN:

26325

American (AMR)

AF:

0.0000286

AC:

AN:

34953

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19264

East Asian (EAS)

AF:

0.000932

AC:

AN:

30055

South Asian (SAS)

AF:

0.00

AC:

AN:

53388

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40429

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4122

European-Non Finnish (NFE)

AF:

0.00000715

AC:

AN:

838930

Other (OTH)

AF:

0.00

AC:

AN:

45875

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000714

AC:

AN:

112081

Hom.:

Cov.:

AF XY:

0.0000876

AC XY:

AN XY:

34247

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30891

American (AMR)

AF:

0.0000946

AC:

AN:

10567

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.000844

AC:

AN:

3556

South Asian (SAS)

AF:

0.00

AC:

AN:

2709

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53222

Other (OTH)

AF:

0.000657

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000291

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.047

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.74

M_CAP

Benign

0.0027

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.77

PhyloP100

1.8

PrimateAI

Benign

0.29

PROVEAN

Benign

1.4

REVEL

Benign

0.056

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.030

Vest4

0.024

MVP

0.21

MPC

0.61

ClinPred

0.011

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.057

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over