Variant X-15455895-C-T 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.433G>A(p.Asp145Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,209,455 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 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 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 12 hem. )

Consequence

PIR
NM_001018109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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:

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=0.047415763).

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIR	NM_001018109.3 linkuse as main transcript	c.433G>A	p.Asp145Asn	missense_variant	5/10	ENST00000380420.10	NP_001018119.1	O00625A0A024RBX6
PIR	NM_003662.4 linkuse as main transcript	c.433G>A	p.Asp145Asn	missense_variant	5/10		NP_003653.1	O00625A0A024RBX6
PIR-FIGF	NR_037859.2 linkuse as main transcript	n.485G>A		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.433G>A	p.Asp145Asn	missense_variant	5/10	1	NM_001018109.3	ENSP00000369785.5	O00625
PIR	ENST00000380421.3 linkuse as main transcript	c.433G>A	p.Asp145Asn	missense_variant	5/10	1		ENSP00000369786.3	O00625
PIR	ENST00000476381.5 linkuse as main transcript	n.383G>A		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112177

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34327

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:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000872

AC:

AN:

183464

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

67902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000839

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000210

AC:

AN:

1097278

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

362650

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000388

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112177

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34327

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:

0.000370

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000223

Hom.:

ExAC

AF:

0.000115

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

Oct 05, 2023

The c.433G>A (p.D145N) alteration is located in exon 5 (coding exon 4) of the PIR gene. This alteration results from a G to A substitution at nucleotide position 433, causing the aspartic acid (D) at amino acid position 145 to be replaced by an asparagine (N). 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

0.090

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

T;T

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.85

.;D

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.1

D;D

REVEL

Benign

0.069

Sift

Benign

0.054

T;T

Sift4G

Uncertain

0.058

T;T

Polyphen

0.0

B;B

Vest4

0.026

MutPred

0.29

Loss of ubiquitination at K144 (P = 0.0613);Loss of ubiquitination at K144 (P = 0.0613);

MVP

0.41

MPC

0.024

ClinPred

0.080

GERP RS

2.7

Varity_R

0.39

gMVP

0.45

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