X-15415414-T-C

Variant names:

• chrX-15415414-T-C
• rs5935970
• NM_001018109.3:c.566-7864A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001018109.3(PIR):​c.566-7864A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (17363 hom., 21089 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: PIR NM_001018109.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 1 publications found

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-FIGF (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIR	NM_001018109.3	c.566-7864A>G		intron_variant	Intron 6 of 9	ENST00000380420.10	NP_001018119.1
PIR	NM_003662.4	c.566-7864A>G		intron_variant	Intron 6 of 9		NP_003653.1
PIR-FIGF	NR_037859.2	n.618-7864A>G		intron_variant	Intron 5 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIR	ENST00000380420.10	c.566-7864A>G		intron_variant	Intron 6 of 9	1	NM_001018109.3	ENSP00000369785.5
PIR	ENST00000380421.3	c.566-7864A>G		intron_variant	Intron 6 of 9	1		ENSP00000369786.3

Frequencies

GnomAD3 genomes AF: 0.658 AC: 72504 AN: 110149 Hom.: 17368 Cov.: 23

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.652

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.658 AC: 72518 AN: 110200 Hom.: 17363 Cov.: 23 AF XY: 0.650 AC XY: 21089 AN XY: 32448

African (AFR) AF: 0.572 AC: 17363 AN: 30349

American (AMR) AF: 0.561 AC: 5819 AN: 10367

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 1664 AN: 2608

East Asian (EAS) AF: 0.483 AC: 1700 AN: 3521

South Asian (SAS) AF: 0.518 AC: 1343 AN: 2594

European-Finnish (FIN) AF: 0.805 AC: 4587 AN: 5695

Middle Eastern (MID) AF: 0.667 AC: 142 AN: 213

European-Non Finnish (NFE) AF: 0.729 AC: 38427 AN: 52689

Other (OTH) AF: 0.655 AC: 973 AN: 1486

Alfa AF: 0.678 Hom.: 11883

Bravo AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.65
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5935970; hg19: chrX-15433536;