Genetic Variant PABIR3:p.Val27Ile (chrX-134807677-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001388447.1(PABIR3):c.79G>A(p.Val27Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,091,452 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Consequence

PABIR3
NM_001388447.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0320

Publications

0 publications found

Variant links:

Genes affected

PABIR3 (HGNC:25202): (PABIR family member 3) Predicted to enable protein serine/threonine phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

PABIR3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14190051).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR3	NM_001388447.1 link	c.79G>A	p.Val27Ile	missense_variant	Exon 2 of 11	ENST00000645433.2	NP_001375376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR3	ENST00000645433.2 link	c.79G>A	p.Val27Ile	missense_variant	Exon 2 of 11		NM_001388447.1	ENSP00000496338.1		A0A2R8Y7S4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000564

AC:

AN:

177408

AF XY:

0.0000161

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1091452

Hom.:

Cov.:

AF XY:

0.00000840

AC XY:

AN XY:

357264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26277

American (AMR)

AF:

0.00

AC:

AN:

34789

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19134

East Asian (EAS)

AF:

0.00

AC:

AN:

29905

South Asian (SAS)

AF:

0.000113

AC:

AN:

52966

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4097

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

838131

Other (OTH)

AF:

0.00

AC:

AN:

45807

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.79G>A (p.V27I) alteration is located in exon 1 (coding exon 1) of the FAM122C gene. This alteration results from a G to A substitution at nucleotide position 79, causing the valine (V) at amino acid position 27 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.022

.;.;.;.;.;.;T;.;T;T;.;.

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.90

.;D;D;D;T;D;D;D;.;D;D;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;.;.;.;.;.;N;N;.;.;.;.

PhyloP100

-0.032

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.32

.;.;N;.;.;.;N;N;.;.;.;.

REVEL

Benign

0.041

Sift

Benign

0.048

.;.;D;.;.;.;D;D;.;.;.;.

Sift4G

Uncertain

0.055

.;.;T;.;.;D;T;T;.;.;.;.

Polyphen

0.059, 0.033

.;.;.;.;.;.;B;B;.;.;.;.

Vest4

0.13, 0.14, 0.099, 0.10

MutPred

0.45

.;.;.;Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);Gain of catalytic residue at L32 (P = 0.0685);

MVP

0.12

MPC

0.14

ClinPred

0.049

GERP RS

-0.98

PromoterAI

-0.00020

Neutral

(source)

Varity_R

0.047

gMVP

0.23

Mutation Taster

=98/2

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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X-134807677-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over