Variant X-15456011-C-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.317G>T(p.Cys106Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000595 in 1,209,905 control chromosomes in the GnomAD database, including 2 homozygotes. There are 189 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., 78 hem., cov: 24)

Exomes 𝑓: 0.00037 ( 0 hom. 111 hem. )

Consequence

PIR
NM_001018109.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.58

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-FIGF (HGNC:):

PIR-FIGF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008328557).

BP6

Variant X-15456011-C-A is Benign according to our data. Variant chrX-15456011-C-A is described in ClinVar as [Benign]. Clinvar id is 717759.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIR	NM_001018109.3 linkuse as main transcript	c.317G>T	p.Cys106Phe	missense_variant	5/10	ENST00000380420.10
PIR-FIGF	NR_037859.2 linkuse as main transcript	n.369G>T		non_coding_transcript_exon_variant	4/15
PIR	NM_003662.4 linkuse as main transcript	c.317G>T	p.Cys106Phe	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIR	ENST00000380420.10 linkuse as main transcript	c.317G>T	p.Cys106Phe	missense_variant	5/10	1	NM_001018109.3	P1
PIR	ENST00000380421.3 linkuse as main transcript	c.317G>T	p.Cys106Phe	missense_variant	5/10	1		P1
PIR	ENST00000476381.5 linkuse as main transcript	n.267G>T		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.00278

AC:

312

AN:

112141

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

AN XY:

34303

show subpopulations

Gnomad AFR

AF:

0.00996

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

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:

0.0000188

Gnomad OTH

AF:

0.00131

GnomAD3 exomes

AF:

0.000988

AC:

181

AN:

183291

Hom.:

AF XY:

0.000753

AC XY:

AN XY:

67757

show subpopulations

Gnomad AFR exome

AF:

0.00927

Gnomad AMR exome

AF:

0.00157

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000371

AC:

407

AN:

1097712

Hom.:

Cov.:

AF XY:

0.000306

AC XY:

111

AN XY:

363098

show subpopulations

Gnomad4 AFR exome

AF:

0.00974

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000369

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.000890

GnomAD4 genome

AF:

0.00279

AC:

313

AN:

112193

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

AN XY:

34365

show subpopulations

Gnomad4 AFR

AF:

0.00997

Gnomad4 AMR

AF:

0.000188

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00130

Alfa

AF:

0.000200

Hom.:

Bravo

AF:

0.00336

ESP6500AA

AF:

0.00913

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000955

AC:

116

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000415

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

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.10

T;T

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.92

.;D

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.63

N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.12

Sift

Benign

0.55

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.51

P;P

Vest4

0.29

MVP

0.75

MPC

0.058

ClinPred

0.012

GERP RS

6.1

Varity_R

0.52

gMVP

0.81

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