X-1305473-G-C

Position:

• chrX-1305473-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172247.3(CSF2RA):​c.974G>C​(p.Arg325Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSF2RA NM_172247.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45

Genes affected

CSF2RA (HGNC:2435): (colony stimulating factor 2 receptor subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric receptor for colony stimulating factor 2, a cytokine which controls the production, differentiation, and function of granulocytes and macrophages. The encoded protein is a member of the cytokine family of receptors. This gene is found in the pseudoautosomal region (PAR) of the X and Y chromosomes. Multiple transcript variants encoding different isoforms have been found for this gene, with some of the isoforms being membrane-bound and others being soluble. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19444337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF2RA	NM_172245.4	c.1071G>C	p.Pro357Pro	synonymous_variant	12/13	ENST00000381529.9	NP_758448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF2RA	ENST00000381529.9	c.1071G>C	p.Pro357Pro	synonymous_variant	12/13	1	NM_172245.4	ENSP00000370940.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	0.26
DANN	Benign	0.42
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Uncertain	0.0041	D
PROVEAN	Benign	0.72	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.17	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.98	D;D
Vest4		0.46
MutPred		0.36		.;Loss of MoRF binding (P = 2e-04);
MVP		0.50
ClinPred		0.12	T
GERP RS		-0.43

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs56960778; hg19: chrX-1424366;