X-134796137-G-A

Variant names:

• chrX-134796137-G-A
• rs141836070
• NM_001387468.1:c.69C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001387468.1(PABIR2):​c.69C>T​(p.Ser23Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,208,483 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 103 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., 6 hem., cov: 21)
  • Exomes 𝑓: 0.00030 (0 hom. 97 hem.)
• Consequence: PABIR2 NM_001387468.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.27
• 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]

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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-134796137-G-A is Benign according to our data. Variant chrX-134796137-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.27 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 1 of 10	ENST00000343004.10	NP_001374397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR2	ENST00000343004.10	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 1 of 10	1	NM_001387468.1	ENSP00000339207.6

Frequencies

GnomAD3 genomes AF: 0.000190 AC: 21 AN: 110441 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000965

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: 0.000360

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 22 AN: 183188 AF XY: 0.000118

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: 0.000126

Gnomad NFE exome AF: 0.000244

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000301 AC: 330 AN: 1097993 Hom.: 0 Cov.: 30 AF XY: 0.000267 AC XY: 97 AN XY: 363361

African (AFR) AF: 0.0000379 AC: 1 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 54143

European-Finnish (FIN) AF: 0.000148 AC: 6 AN: 40451

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.000374 AC: 315 AN: 841983

Other (OTH) AF: 0.000174 AC: 8 AN: 46089

GnomAD4 genome AF: 0.000190 AC: 21 AN: 110490 Hom.: 0 Cov.: 21 AF XY: 0.000183 AC XY: 6 AN XY: 32706

African (AFR) AF: 0.0000330 AC: 1 AN: 30322

American (AMR) AF: 0.0000964 AC: 1 AN: 10372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3500

South Asian (SAS) AF: 0.00 AC: 0 AN: 2589

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000360 AC: 19 AN: 52844

Other (OTH) AF: 0.00 AC: 0 AN: 1498

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.000159

EpiCase AF: 0.000546

EpiControl AF: 0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PABIR2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.1
DANN	Benign	0.70
PhyloP100		2.3
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=92/8	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: rs141836070; hg19: chrX-133930167;