Genetic Variant NM_001387468.1:c.199C>T (chrX-134789615-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001387468.1(PABIR2):c.199C>T(p.Arg67Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00144 in 1,153,224 control chromosomes in the GnomAD database, including 1 homozygotes. There are 535 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 43 hem., cov: 24)

Exomes 𝑓: 0.0015 ( 1 hom. 492 hem. )

Consequence

PABIR2
NM_001387468.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

Publications

1 publications found

Variant links:

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]

PABIR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009171367).

BS2

High Hemizygotes in GnomAd4 at 43 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR2	NM_001387468.1 link	c.199C>T	p.Arg67Cys	missense_variant	Exon 3 of 10	ENST00000343004.10	NP_001374397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR2	ENST00000343004.10 link	c.199C>T	p.Arg67Cys	missense_variant	Exon 3 of 10	1	NM_001387468.1	ENSP00000339207.6		G1UD79

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

135

AN:

112380

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00189

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.000661

GnomAD2 exomes

AF:

0.00137

AC:

144

AN:

104832

AF XY:

0.00129

show subpopulations

Gnomad AFR exome

AF:

0.000158

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000188

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00157

GnomAD4 exome

AF:

0.00147

AC:

1525

AN:

1040792

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

492

AN XY:

339178

show subpopulations

African (AFR)

AF:

0.000161

AC:

AN:

24835

American (AMR)

AF:

0.00170

AC:

AN:

27704

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

18597

East Asian (EAS)

AF:

0.00

AC:

AN:

27101

South Asian (SAS)

AF:

0.0000404

AC:

AN:

49445

European-Finnish (FIN)

AF:

0.0000746

AC:

AN:

26819

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3996

European-Non Finnish (NFE)

AF:

0.00170

AC:

1391

AN:

818009

Other (OTH)

AF:

0.00117

AC:

AN:

44286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

100

150

200

250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00120

AC:

135

AN:

112432

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

34616

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

31004

American (AMR)

AF:

0.00379

AC:

AN:

10564

Ashkenazi Jewish (ASJ)

AF:

0.00189

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3599

South Asian (SAS)

AF:

0.00

AC:

AN:

2762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00156

AC:

AN:

53349

Other (OTH)

AF:

0.000653

AC:

AN:

1531

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00128

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00167

AC:

ExAC

AF:

0.000607

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 26, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.199C>T (p.R67C) alteration is located in exon 3 (coding exon 3) of the FAM122B gene. This alteration results from a C to T substitution at nucleotide position 199, causing the arginine (R) at amino acid position 67 to be replaced by a cysteine (C). 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

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;.;.;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

D;D;D;.

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.0092

T;T;T;T

MetaSVM

Benign

-0.64

PhyloP100

4.5

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.9

D;D;.;.

REVEL

Benign

0.10

Sift

Uncertain

0.0060

D;D;.;.

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.038

.;.;B;.

Vest4

0.27

MVP

0.52

MPC

1.8

ClinPred

0.068

GERP RS

4.2

gMVP

0.35

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

Publications

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NM_001387468.1:c.199C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over