X-15397459-A-G

Position:

chrX-15397459-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001018109.3(PIR):c.683T>C(p.Val228Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00483 in 1,182,639 control chromosomes in the GnomAD database, including 159 homozygotes. There are 1,503 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.024 ( 79 hom., 701 hem., cov: 23)

Exomes 𝑓: 0.0028 ( 80 hom. 802 hem. )

Consequence

PIR
NM_001018109.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.61

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028369129).

BP6

Variant X-15397459-A-G is Benign according to our data. Variant chrX-15397459-A-G is described in ClinVar as [Benign]. Clinvar id is 778979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIR	NM_001018109.3 linkuse as main transcript	c.683T>C	p.Val228Ala	missense_variant	8/10	ENST00000380420.10	NP_001018119.1	O00625A0A024RBX6
PIR	NM_003662.4 linkuse as main transcript	c.683T>C	p.Val228Ala	missense_variant	8/10		NP_003653.1	O00625A0A024RBX6
PIR-FIGF	NR_037859.2 linkuse as main transcript	n.988T>C		non_coding_transcript_exon_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PIR	ENST00000380420.10 linkuse as main transcript	c.683T>C	p.Val228Ala	missense_variant	8/10	1	NM_001018109.3	ENSP00000369785.5	O00625
PIR	ENST00000380421.3 linkuse as main transcript	c.683T>C	p.Val228Ala	missense_variant	8/10	1		ENSP00000369786.3	O00625
PIR	ENST00000484433.1 linkuse as main transcript	n.118T>C		non_coding_transcript_exon_variant	2/3	3
PIR	ENST00000492432.5 linkuse as main transcript	n.221T>C		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

2668

AN:

111737

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

697

AN XY:

33911

show subpopulations

Gnomad AFR

AF:

0.0804

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00795

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000452

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00711

AC:

1302

AN:

183068

Hom.:

AF XY:

0.00509

AC XY:

344

AN XY:

67522

show subpopulations

Gnomad AFR exome

AF:

0.0843

Gnomad AMR exome

AF:

0.00377

Gnomad ASJ exome

AF:

0.00589

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000211

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000342

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00283

AC:

3035

AN:

1070850

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

802

AN XY:

339958

show subpopulations

Gnomad4 AFR exome

AF:

0.0852

Gnomad4 AMR exome

AF:

0.00452

Gnomad4 ASJ exome

AF:

0.00666

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000285

Gnomad4 OTH exome

AF:

0.00584

GnomAD4 genome

AF:

0.0239

AC:

2674

AN:

111789

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

701

AN XY:

33973

show subpopulations

Gnomad4 AFR

AF:

0.0804

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.00795

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000452

Gnomad4 OTH

AF:

0.0164

Alfa

AF:

0.00590

Hom.:

102

Bravo

AF:

0.0283

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.0808

AC:

310

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.00834

AC:

1013

EpiCase

AF:

0.000328

EpiControl

AF:

0.000713

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.76

.;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.064

Sift

Benign

0.34

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.29

B;B

Vest4

0.14

MVP

0.86

MPC

0.040

ClinPred

0.018

GERP RS

5.9

Varity_R

0.61

gMVP

0.67

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