Genetic Variant NM_001387468.1:c.271C>G (chrX-134789230-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001387468.1(PABIR2):c.271C>G(p.His91Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,210,928 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000038 ( 0 hom. 12 hem. )

Consequence

PABIR2
NM_001387468.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1 link	c.271C>G	p.His91Asp	missense_variant	Exon 4 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.271C>G	p.His91Asp	missense_variant	Exon 4 of 10	1	NM_001387468.1	ENSP00000339207.6		G1UD79

Frequencies

GnomAD3 genomes

AF:

0.0000798

AC:

AN:

112731

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000941

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:

0.000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000927

AC:

AN:

183423

AF XY:

0.0000884

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:

0.000208

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000382

AC:

AN:

1098197

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363563

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26402

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30199

South Asian (SAS)

AF:

0.00

AC:

AN:

54143

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000475

AC:

AN:

842101

Other (OTH)

AF:

0.0000434

AC:

AN:

46093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000798

AC:

AN:

112731

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34867

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31050

American (AMR)

AF:

0.0000941

AC:

AN:

10632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3613

South Asian (SAS)

AF:

0.00

AC:

AN:

2785

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6193

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

53358

Other (OTH)

AF:

0.00

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.271C>G (p.H91D) alteration is located in exon 4 (coding exon 4) of the FAM122B gene. This alteration results from a C to G substitution at nucleotide position 271, causing the histidine (H) at amino acid position 91 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

D;T;.;.;.;T

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.89

D;T;D;T;D;.

M_CAP

Pathogenic

0.36

MetaRNN

Uncertain

0.49

T;T;T;T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.5

M;.;.;M;.;.

PhyloP100

5.2

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.4

D;D;D;D;.;.

REVEL

Benign

0.28

Sift

Uncertain

0.0040

D;D;D;D;.;.

Sift4G

Uncertain

0.021

D;D;D;D;D;D

Polyphen

0.22

B;.;.;B;P;.

Vest4

0.57

MutPred

0.17

Gain of phosphorylation at T70 (P = 0.1123);.;.;Gain of phosphorylation at T70 (P = 0.1123);.;.;

MVP

0.67

MPC

0.98

ClinPred

0.45

GERP RS

5.0

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.57

gMVP

0.91

Mutation Taster

=96/4

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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NM_001387468.1:c.271C>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