X-134814782-A-G

Variant names:

• chrX-134814782-A-G
• rs781112656
• NM_001388447.1:c.122A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001388447.1(PABIR3):​c.122A>G​(p.Gln41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,072,981 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: PABIR3 NM_001388447.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.862
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19523063).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR3	NM_001388447.1	c.122A>G	p.Gln41Arg	missense_variant	Exon 3 of 11	ENST00000645433.2	NP_001375376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR3	ENST00000645433.2	c.122A>G	p.Gln41Arg	missense_variant	Exon 3 of 11		NM_001388447.1	ENSP00000496338.1

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112096 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000948

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000484 AC: 8 AN: 165138 AF XY: 0.0000365

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000351

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: 0.0000103 AC: 11 AN: 1072981 Hom.: 0 Cov.: 26 AF XY: 0.00000871 AC XY: 3 AN XY: 344445

African (AFR) AF: 0.00 AC: 0 AN: 25265

American (AMR) AF: 0.000350 AC: 11 AN: 31410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18649

East Asian (EAS) AF: 0.00 AC: 0 AN: 29821

South Asian (SAS) AF: 0.00 AC: 0 AN: 50973

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40217

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 827569

Other (OTH) AF: 0.00 AC: 0 AN: 45044

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000892 AC: 1 AN: 112096 Hom.: 0 Cov.: 23 AF XY: 0.0000292 AC XY: 1 AN XY: 34270

African (AFR) AF: 0.00 AC: 0 AN: 30847

American (AMR) AF: 0.0000948 AC: 1 AN: 10551

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3612

South Asian (SAS) AF: 0.00 AC: 0 AN: 2746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6049

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53215

Other (OTH) AF: 0.00 AC: 0 AN: 1505

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000659 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.122A>G (p.Q41R) alteration is located in exon 2 (coding exon 2) of the FAM122C gene. This alteration results from a A to G substitution at nucleotide position 122, causing the glutamine (Q) at amino acid position 41 to be replaced by an arginine (R). 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	Benign	-0.34	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.11	.;.;.;.;T;.;.
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.61	T;T;T;T;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	2.0	.;.;.;.;M;M;.
PhyloP100		0.86
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D;.;.;.;D;D;.
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;.;.;.;D;D;.
Sift4G	Uncertain	0.010	D;.;.;D;D;D;.
Polyphen		1.0, 1.0	.;.;.;.;D;D;.
Vest4		0.46
MutPred		0.48		.;Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);Gain of MoRF binding (P = 0.0165);
MVP		0.40
MPC		0.17
ClinPred		0.25	T
GERP RS		1.4
Varity_R		0.44
gMVP		0.34
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs781112656; hg19: chrX-133948812;