rs545530472

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001018109.3(PIR):c.106C>A(p.Leu36Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,128,400 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 90 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 0.000098 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 0 hom. 85 hem. )

Consequence

PIR
NM_001018109.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

0 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 links:

BMX (HGNC:1079): (BMX non-receptor tyrosine kinase) This gene encodes a non-receptor tyrosine kinase belonging to the Tec kinase family. The protein contains a PH-like domain, which mediates membrane targeting by binding to phosphatidylinositol 3,4,5-triphosphate (PIP3), and a SH2 domain that binds to tyrosine-phosphorylated proteins and functions in signal transduction. The protein is implicated in several signal transduction pathways including the Stat pathway, and regulates differentiation and tumorigenicity of several types of cancer cells. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

BMX 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01931864).

BS2

High Hemizygotes in GnomAd4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018109.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIR	NM_001018109.3	MANE Select	c.106C>A	p.Leu36Met	missense	Exon 3 of 10	NP_001018119.1	O00625
PIR	NM_003662.4		c.106C>A	p.Leu36Met	missense	Exon 3 of 10	NP_003653.1	O00625
PIR-FIGF	NR_037859.2		n.158C>A		non_coding_transcript_exon	Exon 2 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PIR	ENST00000380420.10	TSL:1 MANE Select	c.106C>A	p.Leu36Met	missense	Exon 3 of 10	ENSP00000369785.5	O00625
PIR	ENST00000380421.3	TSL:1	c.106C>A	p.Leu36Met	missense	Exon 3 of 10	ENSP00000369786.3	O00625
PIR	ENST00000909226.1		c.106C>A	p.Leu36Met	missense	Exon 3 of 11	ENSP00000579285.1

Frequencies

GnomAD3 genomes

AF:

0.0000983

AC:

AN:

111871

Hom.:

Cov.:

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:

0.00404

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000201

AC:

AN:

164133

AF XY:

0.000423

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000145

AC:

147

AN:

1016475

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

AN XY:

297433

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24497

American (AMR)

AF:

0.00

AC:

AN:

32602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18463

East Asian (EAS)

AF:

0.0000341

AC:

AN:

29351

South Asian (SAS)

AF:

0.00292

AC:

142

AN:

48671

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40181

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3639

European-Non Finnish (NFE)

AF:

0.00000129

AC:

AN:

775795

Other (OTH)

AF:

0.0000693

AC:

AN:

43276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000983

AC:

AN:

111925

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

34117

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30818

American (AMR)

AF:

0.00

AC:

AN:

10547

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3594

South Asian (SAS)

AF:

0.00405

AC:

AN:

2715

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6029

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53151

Other (OTH)

AF:

0.00

AC:

AN:

1524

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000412

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.059

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.2

PhyloP100

1.5

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.29

Sift

Uncertain

0.013

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.15

MutPred

0.61

Gain of ubiquitination at K34 (P = 0.046)

MVP

0.73

MPC

0.20

ClinPred

0.15

GERP RS

4.4

Varity_R

0.68

gMVP

0.47

Mutation Taster

=83/17

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over