CSF3R p.Ser575Cys

Variant names:

• chr1-36467962-G-C
• NM_000760.4:c.1724C>G
• CSF3R p.Ser575Cys

Your query was ambiguous. Multiple possible variants found:

• chr1-36467962-G-C
• chr1-36467961-GG-AC

Variant summary

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

The NM_000760.4(CSF3R):​c.1724C>G​(p.Ser575Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. S575P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CSF3R NM_000760.4 missense, splice_region
• Scores: Splicing: ADA: 0.0006198
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854
• Publications: 0 publications found

Genes affected

CSF3R (HGNC:2439): (colony stimulating factor 3 receptor) The protein encoded by this gene is the receptor for colony stimulating factor 3, a cytokine that controls the production, differentiation, and function of granulocytes. The encoded protein, which is a member of the family of cytokine receptors, may also function in some cell surface adhesion or recognition processes. Alternatively spliced transcript variants have been described. Mutations in this gene are a cause of Kostmann syndrome, also known as severe congenital neutropenia. [provided by RefSeq, Aug 2010]

CSF3R Gene-Disease associations (from GenCC):

• hereditary neutrophilia

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• autosomal recessive severe congenital neutropenia due to CSF3R deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000297367 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000760.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3R	NM_000760.4	MANE Select	c.1724C>G	p.Ser575Cys	missense splice_region	Exon 14 of 17	NP_000751.1	Q99062-1
	CSF3R	NM_156039.3		c.1724C>G	p.Ser575Cys	missense splice_region	Exon 14 of 17	NP_724781.1	Q99062-3
	CSF3R	NM_172313.3		c.1724C>G	p.Ser575Cys	missense splice_region	Exon 14 of 18	NP_758519.1	Q99062-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSF3R	ENST00000373106.6	TSL:1 MANE Select	c.1724C>G	p.Ser575Cys	missense splice_region	Exon 14 of 17	ENSP00000362198.2	Q99062-1
	CSF3R	ENST00000373103.5	TSL:1	c.1724C>G	p.Ser575Cys	missense splice_region	Exon 14 of 17	ENSP00000362195.1	Q99062-3
	CSF3R	ENST00000373104.5	TSL:1	c.1724C>G	p.Ser575Cys	missense splice_region	Exon 14 of 18	ENSP00000362196.1	Q99062-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.85
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.27
Sift	Benign	0.11	T
Sift4G	Benign	0.11	T
Varity_R		0.33
gMVP		0.83
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00062
dbscSNV1_RF	Benign	0.16
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-36933563;