NM_001387468.1:c.506G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001387468.1(PABIR2):​c.506G>A​(p.Ser169Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,893 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

PABIR2
NM_001387468.1 missense

Scores

1
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.49

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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3056615).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PABIR2NM_001387468.1 linkc.506G>A p.Ser169Asn missense_variant Exon 8 of 10 ENST00000343004.10 NP_001374397.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PABIR2ENST00000343004.10 linkc.506G>A p.Ser169Asn missense_variant Exon 8 of 10 1 NM_001387468.1 ENSP00000339207.6 G1UD79

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
9.12e-7
AC:
1
AN:
1096893
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
362315
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
26377
American (AMR)
AF:
0.00
AC:
0
AN:
35172
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19361
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30185
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54055
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40491
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3974
European-Non Finnish (NFE)
AF:
0.00000119
AC:
1
AN:
841238
Other (OTH)
AF:
0.00
AC:
0
AN:
46040
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
23

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 18, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.503G>A (p.S168N) alteration is located in exon 8 (coding exon 8) of the FAM122B gene. This alteration results from a G to A substitution at nucleotide position 503, causing the serine (S) at amino acid position 168 to be replaced by an asparagine (N). 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
0.21
BayesDel_addAF
Benign
0.0023
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.59
D;T;.;.;.;T
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.80
T;T;T;T;T;.
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.31
T;T;T;T;T;T
MetaSVM
Uncertain
0.16
D
MutationAssessor
Uncertain
2.8
M;.;.;.;.;.
PhyloP100
1.5
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-2.4
N;.;N;N;.;.
REVEL
Uncertain
0.33
Sift
Uncertain
0.0010
D;.;D;D;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;.;.;D;D;.
Vest4
0.23
MutPred
0.31
Loss of phosphorylation at S149 (P = 0.0013);.;.;.;.;.;
MVP
0.56
MPC
0.59
ClinPred
0.96
D
GERP RS
5.7
Varity_R
0.67
gMVP
0.62
Mutation Taster
=48/52
disease causing

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

Other links and lift over

hg19: chrX-133919972; API