Variant X-15407529-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001018109.3(PIR):c.587C>T(p.Thr196Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,200,965 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 55 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 0.000062 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 53 hem. )

Consequence

PIR
NM_001018109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04088974).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIR	NM_001018109.3 linkuse as main transcript	c.587C>T	p.Thr196Met	missense_variant	7/10	ENST00000380420.10
PIR-FIGF	NR_037859.2 linkuse as main transcript	n.639C>T		non_coding_transcript_exon_variant	6/15
PIR	NM_003662.4 linkuse as main transcript	c.587C>T	p.Thr196Met	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIR	ENST00000380420.10 linkuse as main transcript	c.587C>T	p.Thr196Met	missense_variant	7/10	1	NM_001018109.3	P1
PIR	ENST00000380421.3 linkuse as main transcript	c.587C>T	p.Thr196Met	missense_variant	7/10	1		P1
PIR	ENST00000484433.1 linkuse as main transcript	n.22C>T		non_coding_transcript_exon_variant	1/3	3
PIR	ENST00000492432.5 linkuse as main transcript	n.125C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000623

AC:

AN:

112344

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

34528

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00183

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000240

AC:

AN:

183197

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

67657

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00205

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000111

AC:

121

AN:

1088564

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

354632

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000166

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.0000420

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

AF:

0.0000623

AC:

AN:

112401

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

34593

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00183

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000555

Hom.:

Bravo

AF:

0.0000453

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

The c.587C>T (p.T196M) alteration is located in exon 7 (coding exon 6) of the PIR gene. This alteration results from a C to T substitution at nucleotide position 587, causing the threonine (T) at amino acid position 196 to be replaced by a methionine (M). 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

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

.;D

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

1.0

D;D

Vest4

0.20

MVP

0.65

MPC

0.19

ClinPred

0.12

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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