chrX-134788809-G-A

Variant names:

• chrX-134788809-G-A
• rs753150171
• NM_001387468.1:c.356C>T

Variant summary

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

The NM_001387468.1(PABIR2):​c.356C>T​(p.Pro119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,205,365 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000019 (0 hom. 8 hem.)
• Consequence: PABIR2 NM_001387468.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06961411).
• BS2: High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1	c.356C>T	p.Pro119Leu	missense_variant	Exon 6 of 10	ENST00000343004.10	NP_001374397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR2	ENST00000343004.10	c.356C>T	p.Pro119Leu	missense_variant	Exon 6 of 10	1	NM_001387468.1	ENSP00000339207.6

Frequencies

GnomAD3 genomes AF: 0.0000181 AC: 2 AN: 110440 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000329

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000166 AC: 3 AN: 180206 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000372

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000732

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 21 AN: 1094925 Hom.: 0 Cov.: 29 AF XY: 0.0000222 AC XY: 8 AN XY: 360387

African (AFR) AF: 0.00 AC: 0 AN: 26327

American (AMR) AF: 0.0000286 AC: 1 AN: 34988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19310

East Asian (EAS) AF: 0.00 AC: 0 AN: 30120

South Asian (SAS) AF: 0.00 AC: 0 AN: 53616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40488

Middle Eastern (MID) AF: 0.00147 AC: 6 AN: 4070

European-Non Finnish (NFE) AF: 0.0000167 AC: 14 AN: 840050

Other (OTH) AF: 0.00 AC: 0 AN: 45956

GnomAD4 genome AF: 0.0000181 AC: 2 AN: 110440 Hom.: 0 Cov.: 22 AF XY: 0.0000306 AC XY: 1 AN XY: 32716

African (AFR) AF: 0.0000329 AC: 1 AN: 30354

American (AMR) AF: 0.00 AC: 0 AN: 10183

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3591

South Asian (SAS) AF: 0.00 AC: 0 AN: 2667

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52970

Other (OTH) AF: 0.00 AC: 0 AN: 1491

Alfa AF: 0.000375 Hom.: 1

Bravo AF: 0.0000642

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000600

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.356C>T (p.P119L) alteration is located in exon 6 (coding exon 6) of the FAM122B gene. This alteration results from a C to T substitution at nucleotide position 356, causing the proline (P) at amino acid position 119 to be replaced by a leucine (L). 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	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.74
DEOGEN2	Benign	0.13	T;T;.;.;.;T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;.
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.070	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;.;M;.;.
PhyloP100		2.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N;N;N;N;.;.
REVEL	Benign	0.079
Sift	Uncertain	0.0080	D;D;D;T;.;.
Sift4G	Uncertain	0.012	D;D;D;D;D;D
Polyphen		0.43	B;.;.;B;P;.
Vest4		0.23
MutPred		0.20		Loss of loop (P = 0.0022);.;.;Loss of loop (P = 0.0022);.;.;
MVP		0.068
MPC		0.64
ClinPred		0.074	T
GERP RS		-0.89
Varity_R		0.082
gMVP		0.43
Mutation Taster		=91/9	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: rs753150171; hg19: chrX-133922839;