X-15390251-C-T

Position:

chrX-15390251-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001018109.3(PIR):c.694G>A(p.Asp232Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00164 in 1,099,752 control chromosomes in the GnomAD database, including 15 homozygotes. There are 460 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 4 hom., 216 hem., cov: 23)

Exomes 𝑓: 0.00099 ( 11 hom. 244 hem. )

Consequence

PIR
NM_001018109.3 missense, splice_region

Scores

Splicing: ADA: 0.8432

Clinical Significance

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

Conservation

PhyloP100: 5.01

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067566335).

BP6

Variant X-15390251-C-T is Benign according to our data. Variant chrX-15390251-C-T is described in ClinVar as [Benign]. Clinvar id is 775779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00749 (835/111541) while in subpopulation AFR AF= 0.0255 (785/30784). AF 95% confidence interval is 0.024. There are 4 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIR	NM_001018109.3 linkuse as main transcript	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	9/10	ENST00000380420.10
PIR-FIGF	NR_037859.2 linkuse as main transcript	n.999G>A		splice_region_variant, non_coding_transcript_exon_variant	9/15
PIR	NM_003662.4 linkuse as main transcript	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIR	ENST00000380420.10 linkuse as main transcript	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	9/10	1	NM_001018109.3	P1
PIR	ENST00000380421.3 linkuse as main transcript	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	9/10	1		P1
PIR	ENST00000484433.1 linkuse as main transcript	n.129G>A		splice_region_variant, non_coding_transcript_exon_variant	3/3	3
PIR	ENST00000492432.5 linkuse as main transcript	n.232G>A		splice_region_variant, non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

832

AN:

111488

Hom.:

Cov.:

AF XY:

0.00638

AC XY:

215

AN XY:

33692

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00257

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00840

Gnomad NFE

AF:

0.000189

Gnomad OTH

AF:

0.00671

GnomAD3 exomes

AF:

0.00222

AC:

361

AN:

162590

Hom.:

AF XY:

0.00134

AC XY:

AN XY:

52374

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000204

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000266

Gnomad OTH exome

AF:

0.00155

GnomAD4 exome

AF:

0.000986

AC:

974

AN:

988211

Hom.:

Cov.:

AF XY:

0.000875

AC XY:

244

AN XY:

278849

show subpopulations

Gnomad4 AFR exome

AF:

0.0282

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.0000554

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000114

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.00230

GnomAD4 genome

AF:

0.00749

AC:

835

AN:

111541

Hom.:

Cov.:

AF XY:

0.00640

AC XY:

216

AN XY:

33755

show subpopulations

Gnomad4 AFR

AF:

0.0255

Gnomad4 AMR

AF:

0.00257

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000189

Gnomad4 OTH

AF:

0.00661

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00883

ESP6500AA

AF:

0.0289

AC:

111

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00260

AC:

316

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 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.057

T;T

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.79

.;T

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.0068

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.16

N;N

REVEL

Benign

0.064

Sift

Benign

0.18

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0010

B;B

Vest4

0.46

MVP

0.38

MPC

0.024

ClinPred

0.0098

GERP RS

5.5

Varity_R

0.24

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.84

dbscSNV1_RF

Benign

0.64

SpliceAI score (max)

0.010

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