NM_001018109.3:c.565+5014T>C

Variant names:

• chrX-15420892-A-G
• rs234495
• NM_001018109.3:c.565+5014T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018109.3(PIR):​c.565+5014T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 110,705 control chromosomes in the GnomAD database, including 4,367 homozygotes. There are 9,684 hemizygotes in GnomAD. 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 0.30 (4367 hom., 9684 hem., cov: 22)
• Consequence: PIR NM_001018109.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.944
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIR	NM_001018109.3	MANE Select	c.565+5014T>C		intron	N/A	NP_001018119.1
	PIR	NM_003662.4		c.565+5014T>C		intron	N/A	NP_003653.1
	PIR-FIGF	NR_037859.2		n.617+5014T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIR	ENST00000380420.10	TSL:1 MANE Select	c.565+5014T>C		intron	N/A	ENSP00000369785.5
	PIR	ENST00000380421.3	TSL:1	c.565+5014T>C		intron	N/A	ENSP00000369786.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 33259 AN: 110652 Hom.: 4366 Cov.: 22

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.301 AC: 33296 AN: 110705 Hom.: 4367 Cov.: 22 AF XY: 0.294 AC XY: 9684 AN XY: 32959

African (AFR) AF: 0.470 AC: 14241 AN: 30303

American (AMR) AF: 0.387 AC: 4025 AN: 10394

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 688 AN: 2638

East Asian (EAS) AF: 0.506 AC: 1772 AN: 3504

South Asian (SAS) AF: 0.446 AC: 1151 AN: 2580

European-Finnish (FIN) AF: 0.127 AC: 760 AN: 5985

Middle Eastern (MID) AF: 0.235 AC: 50 AN: 213

European-Non Finnish (NFE) AF: 0.190 AC: 10077 AN: 52917

Other (OTH) AF: 0.302 AC: 450 AN: 1490

Alfa AF: 0.235 Hom.: 16975

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.60
DANN	Benign	0.37
PhyloP100		-0.94
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: rs234495; hg19: chrX-15439015;