Genetic Variant PABIR3:p.Met199Ile (chrX-134852807-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001388447.1(PABIR3):c.597G>C(p.Met199Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000099 in 1,010,258 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. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.9e-7 ( 0 hom. 0 hem. )

Consequence

PABIR3
NM_001388447.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05892968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR3	NM_001388447.1 link	c.597G>C	p.Met199Ile	missense_variant	Exon 10 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.597G>C	p.Met199Ile	missense_variant	Exon 10 of 11		NM_001388447.1	ENSP00000496338.1		A0A2R8Y7S4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000123

AC:

AN:

81449

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000724

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:

9.90e-7

AC:

AN:

1010258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

316844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23792

American (AMR)

AF:

0.00

AC:

AN:

24203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18032

East Asian (EAS)

AF:

0.00

AC:

AN:

25737

South Asian (SAS)

AF:

0.00

AC:

AN:

44732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3989

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

800438

Other (OTH)

AF:

0.0000232

AC:

AN:

43065

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.353G>C (p.W118S) alteration is located in exon 6 (coding exon 6) of the FAM122C gene. This alteration results from a G to C substitution at nucleotide position 353, causing the tryptophan (W) at amino acid position 118 to be replaced by a serine (S). 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

0.24

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.5

(source)

DANN

Benign

0.87

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.028

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

PhyloP100

0.071

ClinPred

0.087

GERP RS

1.2

Varity_R

0.20

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over