X-15390251-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 23. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIR	NM_001018109.3 link	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	Exon 9 of 10	ENST00000380420.10	NP_001018119.1	O00625A0A024RBX6
PIR	NM_003662.4 link	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	Exon 9 of 10		NP_003653.1	O00625A0A024RBX6
PIR-FIGF	NR_037859.2 link	n.999G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 9 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIR	ENST00000380420.10 link	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	Exon 9 of 10	1	NM_001018109.3	ENSP00000369785.5	O00625
PIR	ENST00000380421.3 link	c.694G>A	p.Asp232Asn	missense_variant, splice_region_variant	Exon 9 of 10	1		ENSP00000369786.3	O00625
PIR	ENST00000484433.1 link	n.129G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 3	3
PIR	ENST00000492432.5 link	n.232G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.00746

AC:

832

AN:

111488

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00222

AC:

361

AN:

162590

AF XY:

0.00134

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 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

AC:

675

AN:

23949

Gnomad4 AMR exome

AF:

0.00197

AC:

AN:

31445

Gnomad4 ASJ exome

AF:

0.0000554

AC:

AN:

18062

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

28584

Gnomad4 SAS exome

AF:

0.000114

AC:

AN:

43976

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

39850

Gnomad4 NFE exome

AF:

0.000153

AC:

116

AN:

756293

Gnomad4 Remaining exome

AF:

0.00230

AC:

AN:

42208

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.0255003

AN:

0.0255003

Gnomad4 AMR

AF:

0.00257

AC:

0.00256556

AN:

0.00256556

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000375

AC:

0.000375375

AN:

0.000375375

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000189

AC:

0.000188747

AN:

0.000188747

Gnomad4 OTH

AF:

0.00661

AC:

0.00661376

AN:

0.00661376

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00287

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 23, 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

0.10

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

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

Mutation Taster

=98/2

polymorphism (auto)

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