Variant chrX-15456039-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001018109.3(PIR):c.289C>T(p.Arg97Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,208,326 control chromosomes in the GnomAD database, including 7 homozygotes. There are 529 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., 47 hem., cov: 24)

Exomes 𝑓: 0.0013 ( 7 hom. 482 hem. )

Consequence

PIR
NM_001018109.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.55

Variant links:

Genes affected

PIR (HGNC:30048): (pirin) This gene encodes a member of the cupin superfamily. The encoded protein is an Fe(II)-containing nuclear protein expressed in all tissues of the body and concentrated within dot-like subnuclear structures. Interactions with nuclear factor I/CCAAT box transcription factor as well as B cell lymphoma 3-encoded oncoprotein suggest the encoded protein may act as a transcriptional cofactor and be involved in the regulation of DNA transcription and replication. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

PIR links:

PIR (HGNC:):

PIR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02541989).

BP6

Variant X-15456039-G-A is Benign according to our data. Variant chrX-15456039-G-A is described in ClinVar as [Benign]. Clinvar id is 717762.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 47 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIR	NM_001018109.3 linkuse as main transcript	c.289C>T	p.Arg97Trp	missense_variant	5/10	ENST00000380420.10	NP_001018119.1	O00625A0A024RBX6
PIR	NM_003662.4 linkuse as main transcript	c.289C>T	p.Arg97Trp	missense_variant	5/10		NP_003653.1	O00625A0A024RBX6
PIR-FIGF	NR_037859.2 linkuse as main transcript	n.341C>T		non_coding_transcript_exon_variant	4/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIR	ENST00000380420.10 linkuse as main transcript	c.289C>T	p.Arg97Trp	missense_variant	5/10	1	NM_001018109.3	ENSP00000369785.5	O00625
PIR	ENST00000380421.3 linkuse as main transcript	c.289C>T	p.Arg97Trp	missense_variant	5/10	1		ENSP00000369786.3	O00625
PIR	ENST00000476381.5 linkuse as main transcript	n.239C>T		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

144

AN:

112067

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

34233

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.0142

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.000660

GnomAD3 exomes

AF:

0.00215

AC:

393

AN:

182866

Hom.:

AF XY:

0.00239

AC XY:

161

AN XY:

67372

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0169

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00331

GnomAD4 exome

AF:

0.00131

AC:

1435

AN:

1096208

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

482

AN XY:

361762

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0184

Gnomad4 NFE exome

AF:

0.000748

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00128

AC:

144

AN:

112118

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

34294

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.000652

Alfa

AF:

0.000642

Hom.:

Bravo

AF:

0.000374

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00212

AC:

257

EpiCase

AF:

0.000109

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.60

D;D

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;D

MetaRNN

Benign

0.025

T;T

MetaSVM

Uncertain

-0.069

MutationAssessor

Pathogenic

3.5

H;H

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-7.5

D;D

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.49

MVP

0.80

MPC

0.031

ClinPred

0.23

GERP RS

6.1

Varity_R

0.92

gMVP

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over