Genetic Variant PABIR2:p.Ser62Leu (chrX-134789629-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001387468.1(PABIR2):c.185C>T(p.Ser62Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,150,848 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 61 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.00017 ( 0 hom. 59 hem. )

Consequence

PABIR2
NM_001387468.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.50

Publications

0 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3311876).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1 link	c.185C>T	p.Ser62Leu	missense_variant	Exon 3 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.185C>T	p.Ser62Leu	missense_variant	Exon 3 of 10	1	NM_001387468.1	ENSP00000339207.6		G1UD79

Frequencies

GnomAD3 genomes

AF:

0.000115

AC:

AN:

112575

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000206

Gnomad OTH

AF:

0.000662

GnomAD2 exomes

AF:

0.0000580

AC:

AN:

103503

AF XY:

0.0000282

show subpopulations

Gnomad AFR exome

AF:

0.000159

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:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000172

AC:

179

AN:

1038273

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

336809

show subpopulations

African (AFR)

AF:

0.0000404

AC:

AN:

24758

American (AMR)

AF:

0.00

AC:

AN:

27420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18527

East Asian (EAS)

AF:

0.00

AC:

AN:

27073

South Asian (SAS)

AF:

0.00

AC:

AN:

48921

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26797

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3916

European-Non Finnish (NFE)

AF:

0.000216

AC:

176

AN:

816698

Other (OTH)

AF:

0.0000453

AC:

AN:

44163

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000115

AC:

AN:

112575

Hom.:

Cov.:

AF XY:

0.0000576

AC XY:

AN XY:

34725

show subpopulations

African (AFR)

AF:

0.0000322

AC:

AN:

31023

American (AMR)

AF:

0.00

AC:

AN:

10576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3606

South Asian (SAS)

AF:

0.00

AC:

AN:

2769

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6121

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

53394

Other (OTH)

AF:

0.000662

AC:

AN:

1511

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.185C>T (p.S62L) alteration is located in exon 3 (coding exon 3) of the FAM122B gene. This alteration results from a C to T substitution at nucleotide position 185, causing the serine (S) at amino acid position 62 to be replaced by a leucine (L). 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

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

T;.;.;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D;D;.

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.75

PhyloP100

8.5

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.7

N;N;.;.

REVEL

Benign

0.064

Sift

Benign

0.18

T;T;.;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.68

.;.;P;.

Vest4

0.46

MutPred

0.25

Loss of phosphorylation at S62 (P = 0.0205);Loss of phosphorylation at S62 (P = 0.0205);Loss of phosphorylation at S62 (P = 0.0205);Loss of phosphorylation at S62 (P = 0.0205);

MVP

0.43

MPC

0.95

ClinPred

0.14

GERP RS

6.0

gMVP

0.41

Mutation Taster

=95/5

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-134789629-G-A

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