X-15397459-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

PIR links:

PIR-FIGF (HGNC:):

PIR-FIGF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PIR	NM_001018109.3 link	c.683T>C	p.Val228Ala	missense_variant	Exon 8 of 10	ENST00000380420.10	NP_001018119.1	O00625A0A024RBX6
PIR	NM_003662.4 link	c.683T>C	p.Val228Ala	missense_variant	Exon 8 of 10		NP_003653.1	O00625A0A024RBX6
PIR-FIGF	NR_037859.2 link	n.988T>C		non_coding_transcript_exon_variant	Exon 8 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIR	ENST00000380420.10 link	c.683T>C	p.Val228Ala	missense_variant	Exon 8 of 10	1	NM_001018109.3	ENSP00000369785.5	O00625
PIR	ENST00000380421.3 link	c.683T>C	p.Val228Ala	missense_variant	Exon 8 of 10	1		ENSP00000369786.3	O00625
PIR	ENST00000484433.1 link	n.118T>C		non_coding_transcript_exon_variant	Exon 2 of 3	3
PIR	ENST00000492432.5 link	n.221T>C		non_coding_transcript_exon_variant	Exon 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

2668

AN:

111737

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00711

AC:

1302

AN:

183068

AF XY:

0.00509

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 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

African (AFR)

AF:

0.0852

AC:

2215

AN:

26012

American (AMR)

AF:

0.00452

AC:

159

AN:

35162

Ashkenazi Jewish (ASJ)

AF:

0.00666

AC:

128

AN:

19211

East Asian (EAS)

AF:

0.00

AC:

AN:

30066

South Asian (SAS)

AF:

0.000280

AC:

AN:

53548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40525

Middle Eastern (MID)

AF:

0.00514

AC:

AN:

4083

European-Non Finnish (NFE)

AF:

0.000285

AC:

233

AN:

817029

Other (OTH)

AF:

0.00584

AC:

264

AN:

45214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

108

217

325

434

542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0239

AC:

2674

AN:

111789

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

701

AN XY:

33973

show subpopulations

African (AFR)

AF:

0.0804

AC:

2473

AN:

30756

American (AMR)

AF:

0.0124

AC:

131

AN:

10577

Ashkenazi Jewish (ASJ)

AF:

0.00795

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3554

South Asian (SAS)

AF:

0.00

AC:

AN:

2660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6071

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.000452

AC:

AN:

53109

Other (OTH)

AF:

0.0164

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

188

283

377

471

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0139

Hom.:

390

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

3.6

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

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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X-15397459-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over