X-134772210-C-T

Variant names:

• chrX-134772210-C-T
• rs200931503
• NM_001387468.1:c.733G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001387468.1(PABIR2):​c.733G>A​(p.Ala245Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,205,422 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.000034 (0 hom. 9 hem.)
• Consequence: PABIR2 NM_001387468.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.82
• Publications: 5 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01403904).
• BP6: Variant X-134772210-C-T is Benign according to our data. Variant chrX-134772210-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3207806.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1	c.733G>A	p.Ala245Thr	missense_variant	Exon 10 of 10	ENST00000343004.10	NP_001374397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR2	ENST00000343004.10	c.733G>A	p.Ala245Thr	missense_variant	Exon 10 of 10	1	NM_001387468.1	ENSP00000339207.6

Frequencies

GnomAD3 genomes AF: 0.0000714 AC: 8 AN: 112030 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000948

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000841

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.000665

GnomAD2 exomes AF: 0.000106 AC: 19 AN: 179761 AF XY: 0.0000621

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00119

Gnomad FIN exome AF: 0.0000626

Gnomad NFE exome AF: 0.0000248

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000338 AC: 37 AN: 1093341 Hom.: 0 Cov.: 30 AF XY: 0.0000251 AC XY: 9 AN XY: 359219

African (AFR) AF: 0.0000380 AC: 1 AN: 26325

American (AMR) AF: 0.0000286 AC: 1 AN: 34953

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19264

East Asian (EAS) AF: 0.000932 AC: 28 AN: 30055

South Asian (SAS) AF: 0.00 AC: 0 AN: 53388

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40429

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 0.00000715 AC: 6 AN: 838930

Other (OTH) AF: 0.00 AC: 0 AN: 45875

GnomAD4 genome AF: 0.0000714 AC: 8 AN: 112081 Hom.: 0 Cov.: 22 AF XY: 0.0000876 AC XY: 3 AN XY: 34247

African (AFR) AF: 0.0000324 AC: 1 AN: 30891

American (AMR) AF: 0.0000946 AC: 1 AN: 10567

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.000844 AC: 3 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 2709

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6060

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

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53222

Other (OTH) AF: 0.000657 AC: 1 AN: 1523

Alfa AF: 0.0000291 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.000107 AC: 13

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.57
DEOGEN2	Benign	0.047	T;T;.;.;T
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.74	T;T;T;T;.
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.014	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.77	N;.;.;.;.
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.4	N;.;N;.;.
REVEL	Benign	0.056
Sift	Benign	1.0	T;.;T;.;.
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.030	B;.;B;B;.
Vest4		0.024
MVP		0.21
MPC		0.61
ClinPred		0.011	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.057
Mutation Taster		=97/3	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: rs200931503; hg19: chrX-133906240; COSMIC: COSV53231527;