X-134852821-A-G

Variant names:

• chrX-134852821-A-G
• rs201136667
• NM_001388447.1:c.611A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_001388447.1(PABIR3):​c.611A>G​(p.Gln204Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000892 in 1,134,381 control chromosomes in the GnomAD database, including 1 homozygotes. There are 290 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., 15 hem., cov: 23)
  • Exomes 𝑓: 0.00094 (1 hom. 275 hem.)
• Consequence: PABIR3 NM_001388447.1 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.433
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant X-134852821-A-G is Benign according to our data. Variant chrX-134852821-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2457480.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BS2: High Hemizygotes in GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR3	NM_001388447.1	c.611A>G	p.Gln204Arg	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	c.611A>G	p.Gln204Arg	missense_variant	Exon 10 of 11		NM_001388447.1	ENSP00000496338.1

Frequencies

GnomAD3 genomes AF: 0.000483 AC: 54 AN: 111703 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000962

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: 0.000827

Gnomad OTH AF: 0.000662

GnomAD2 exomes AF: 0.000399 AC: 34 AN: 85132 AF XY: 0.000391

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: 0.000911

Gnomad OTH exome AF: 0.000389

GnomAD4 exome AF: 0.000937 AC: 958 AN: 1022627 Hom.: 1 Cov.: 26 AF XY: 0.000842 AC XY: 275 AN XY: 326783

African (AFR) AF: 0.000124 AC: 3 AN: 24102

American (AMR) AF: 0.00 AC: 0 AN: 24865

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18224

East Asian (EAS) AF: 0.00 AC: 0 AN: 25912

South Asian (SAS) AF: 0.00 AC: 0 AN: 45748

European-Finnish (FIN) AF: 0.0000378 AC: 1 AN: 26441

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4033

European-Non Finnish (NFE) AF: 0.00114 AC: 924 AN: 809768

Other (OTH) AF: 0.000689 AC: 30 AN: 43534

GnomAD4 genome AF: 0.000483 AC: 54 AN: 111754 Hom.: 0 Cov.: 23 AF XY: 0.000442 AC XY: 15 AN XY: 33940

African (AFR) AF: 0.000259 AC: 8 AN: 30843

American (AMR) AF: 0.0000961 AC: 1 AN: 10406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3585

South Asian (SAS) AF: 0.00 AC: 0 AN: 2728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5923

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.000827 AC: 44 AN: 53190

Other (OTH) AF: 0.000654 AC: 1 AN: 1530

Alfa AF: 0.000582 Hom.: 5

Bravo AF: 0.000382

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Mar 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.367A>G (p.N123D) alteration is located in exon 6 (coding exon 6) of the FAM122C gene. This alteration results from a A to G substitution at nucleotide position 367, causing the asparagine (N) at amino acid position 123 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PABIR3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0055	T
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0095	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.43
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.024
Sift	Benign	0.37	T
Sift4G	Benign	0.70	T
Polyphen		0.19	B
Vest4		0.069
MVP		0.061
MPC		0.18
ClinPred		0.054	T
GERP RS		2.5
Varity_R		0.11
gMVP		0.025
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201136667; hg19: chrX-133986851;