X-15456011-C-G

Variant names:

• chrX-15456011-C-G
• rs35715407
• NM_001018109.3:c.317G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001018109.3(PIR):​c.317G>C​(p.Cys106Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C106F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 24)
• Consequence: PIR NM_001018109.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1466006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIR	NM_001018109.3	c.317G>C	p.Cys106Ser	missense_variant	Exon 5 of 10	ENST00000380420.10	NP_001018119.1
PIR	NM_003662.4	c.317G>C	p.Cys106Ser	missense_variant	Exon 5 of 10		NP_003653.1
PIR-FIGF	NR_037859.2	n.369G>C		non_coding_transcript_exon_variant	Exon 4 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIR	ENST00000380420.10	c.317G>C	p.Cys106Ser	missense_variant	Exon 5 of 10	1	NM_001018109.3	ENSP00000369785.5
PIR	ENST00000380421.3	c.317G>C	p.Cys106Ser	missense_variant	Exon 5 of 10	1		ENSP00000369786.3
PIR	ENST00000476381.5	n.267G>C		non_coding_transcript_exon_variant	Exon 4 of 5	3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000546 AC: 1 AN: 183291 AF XY: 0.00

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: 0.0000628

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.81
DEOGEN2	Benign	0.043	T;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.85	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.9	N;N
PhyloP100		3.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.99	N;N
REVEL	Benign	0.11
Sift	Benign	0.60	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0080	B;B
Vest4		0.31
MutPred		0.33		Gain of disorder (P = 0.0073);Gain of disorder (P = 0.0073);
MVP		0.76
MPC		0.028
ClinPred		0.26	T
GERP RS		6.1
Varity_R		0.46
gMVP		0.75
Mutation Taster		=99/1	polymorphism

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: rs35715407; hg19: chrX-15474134;