NM_000760.4:c.105C>G

Variant names:

• chr1-36475633-G-C
• NM_000760.4:c.105C>G

Variant summary

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

The NM_000760.4(CSF3R):​c.105C>G​(p.Ile35Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I35V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CSF3R NM_000760.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF3R	NM_000760.4	c.105C>G	p.Ile35Met	missense_variant	Exon 4 of 17	ENST00000373106.6	NP_000751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF3R	ENST00000373106.6	c.105C>G	p.Ile35Met	missense_variant	Exon 4 of 17	1	NM_000760.4	ENSP00000362198.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454820 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;.;.;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.77	.;.;T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.013	D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		0.96	D;P;P;D;P
Vest4		0.34
MutPred		0.69		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.77
MPC		0.77
ClinPred		0.49	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-36941234;