chrX-134789241-C-T

Variant names:

• chrX-134789241-C-T
• NM_001387468.1:c.260G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387468.1(PABIR2):​c.260G>A​(p.Arg87Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: PABIR2 NM_001387468.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1	c.260G>A	p.Arg87Lys	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	c.260G>A	p.Arg87Lys	missense_variant	Exon 4 of 10	1	NM_001387468.1	ENSP00000339207.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.260G>A (p.R87K) alteration is located in exon 4 (coding exon 4) of the FAM122B gene. This alteration results from a G to A substitution at nucleotide position 260, causing the arginine (R) at amino acid position 87 to be replaced by a lysine (K). 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	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;T;.;.;.;T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D;D;D;D;D;.
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.8	M;.;.;M;.;.
PhyloP100		5.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	N;D;D;N;.;.
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D;D;D;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.99	D;.;.;D;D;.
Vest4		0.62
MutPred		0.50		Gain of ubiquitination at R68 (P = 9e-04);.;.;Gain of ubiquitination at R68 (P = 9e-04);.;.;
MVP		0.75
MPC		1.1
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.77
gMVP		0.73
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

hg19: chrX-133923271;