Variant 17-40016955-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172219.3(CSF3):c.611C>T(p.Pro204Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CSF3
NM_172219.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

CSF3 (HGNC:2438): (colony stimulating factor 3) This gene encodes a member of the IL-6 superfamily of cytokines. The encoded cytokine controls the production, differentiation, and function of granulocytes. Granulocytes are a type of white blood cell that are part of the innate immune response. A modified form of this protein is commonly administered to manage chemotherapy-induced neutropenia. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2020]

CSF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.26305294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSF3	NM_172219.3 link	c.611C>T	p.Pro204Leu	missense_variant	5/5	ENST00000394149.8	NP_757373.1	P09919-2Q8N4W3Q6FH65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSF3	ENST00000394149.8 link	c.611C>T	p.Pro204Leu	missense_variant	5/5	1	NM_172219.3	ENSP00000377705.4		P09919-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422984

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704502

show subpopulations

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:

9.15e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.620C>T (p.P207L) alteration is located in exon 5 (coding exon 5) of the CSF3 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the proline (P) at amino acid position 207 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

.;D;.;.;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.65

T;T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.9

.;L;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-4.0

D;D;D;D;.

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

.;D;D;.;.

Vest4

0.085

MutPred

0.55

.;Gain of stability (P = 0.0053);.;.;.;

MVP

0.77

MPC

1.1

ClinPred

0.98

GERP RS

4.1

Varity_R

0.27

gMVP

0.15

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over