chrX-134772210-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001387468.1(PABIR2):​c.733G>T​(p.Ala245Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000747 in 1,205,427 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A245T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000073 (0 hom. 2 hem.)
• Consequence: PABIR2 NM_001387468.1 missense
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0330092).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387468.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABIR2	NM_001387468.1	MANE Select	c.733G>T	p.Ala245Ser	missense	Exon 10 of 10	NP_001374397.1	G1UD79
	PABIR2	NM_001331088.1		c.745G>T	p.Ala249Ser	missense	Exon 10 of 10	NP_001318017.1
	PABIR2	NM_001331089.1		c.742G>T	p.Ala248Ser	missense	Exon 10 of 10	NP_001318018.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABIR2	ENST00000343004.10	TSL:1 MANE Select	c.733G>T	p.Ala245Ser	missense	Exon 10 of 10	ENSP00000339207.6	G1UD79
	PABIR2	ENST00000370790.5	TSL:1	c.673G>T	p.Ala225Ser	missense	Exon 9 of 9	ENSP00000359826.1	Q7Z309-1
	PABIR2	ENST00000896544.1		c.742G>T	p.Ala248Ser	missense	Exon 10 of 10	ENSP00000566603.1

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 112030 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000280

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: 0.0000445 AC: 8 AN: 179761 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000594

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000732 AC: 8 AN: 1093346 Hom.: 0 Cov.: 30 AF XY: 0.00000557 AC XY: 2 AN XY: 359224

African (AFR) AF: 0.00 AC: 0 AN: 26325

American (AMR) AF: 0.00 AC: 0 AN: 34953

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19265

East Asian (EAS) AF: 0.000200 AC: 6 AN: 30056

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53389

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40429

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 838932

Other (OTH) AF: 0.0000218 AC: 1 AN: 45875

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112081 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 34247

African (AFR) AF: 0.00 AC: 0 AN: 30891

American (AMR) AF: 0.00 AC: 0 AN: 10567

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

East Asian (EAS) AF: 0.000281 AC: 1 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: 0.00 AC: 0 AN: 53222

Other (OTH) AF: 0.00 AC: 0 AN: 1523

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.063	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.8
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.060
Sift	Benign	0.049	D
Sift4G	Benign	0.34	T
Polyphen		0.48	P
Vest4		0.073
MutPred		0.078		Gain of phosphorylation at A225 (P = 0.0227)
MVP		0.29
MPC		0.85
ClinPred		0.10	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.078
gMVP		0.058
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: rs200931503; hg19: chrX-133906240;