X-1305473-G-C

Variant names:

• chrX-1305473-G-C
• rs56960778
• ENST00000381500.6:c.974G>C

Variant summary

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

The ENST00000381500.6(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. 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. R325H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSF2RA ENST00000381500.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 0 publications found

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]

CSF2RA Gene-Disease associations (from GenCC):

• surfactant metabolism dysfunction, pulmonary, 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary pulmonary alveolar proteinosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=0.19444337).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381500.6. 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
	CSF2RA	NM_172245.4	MANE Select	c.1071G>C	p.Pro357Pro	synonymous	Exon 12 of 13	NP_758448.1
	CSF2RA	NM_001379167.1		c.974G>C	p.Arg325Pro	missense	Exon 12 of 13	NP_001366096.1
	CSF2RA	NM_001379168.1		c.974G>C	p.Arg325Pro	missense	Exon 10 of 11	NP_001366097.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF2RA	ENST00000381500.6	TSL:1	c.974G>C	p.Arg325Pro	missense	Exon 9 of 10	ENSP00000370911.1
	CSF2RA	ENST00000355805.7	TSL:1	c.674G>C	p.Arg225Pro	missense	Exon 8 of 9	ENSP00000348058.2
	CSF2RA	ENST00000381529.9	TSL:1 MANE Select	c.1071G>C	p.Pro357Pro	synonymous	Exon 12 of 13	ENSP00000370940.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.0041	D
PhyloP100		-2.4
PROVEAN	Benign	0.72	N
REVEL	Uncertain	0.32
Sift	Benign	0.17	T
Sift4G	Benign	0.24	T
Polyphen		0.98	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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs56960778; hg19: chrX-1424366;