NM_000757.6:c.521G>A

Variant names:

• chr1-109921971-G-A
• NM_000757.6:c.521G>A

Variant summary

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

The NM_000757.6(CSF1):​c.521G>A​(p.Ser174Asn) 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. 15/21 in silico tools predict 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. S174I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSF1 NM_000757.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

Genes affected

CSF1 (HGNC:2432): (colony stimulating factor 1) The protein encoded by this gene is a cytokine that controls the production, differentiation, and function of macrophages. The active form of the protein is found extracellularly as a disulfide-linked homodimer, and is thought to be produced by proteolytic cleavage of membrane-bound precursors. The encoded protein may be involved in development of the placenta. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

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=0.2576344).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSF1	NM_000757.6	c.521G>A	p.Ser174Asn	missense_variant	Exon 5 of 9	ENST00000329608.11	NP_000748.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSF1	ENST00000329608.11	c.521G>A	p.Ser174Asn	missense_variant	Exon 5 of 9	1	NM_000757.6	ENSP00000327513.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.25	T;T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	.;T;T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;L;L;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.093
Sift	Uncertain	0.028	D;D;D;D;T
Sift4G	Uncertain	0.046	D;T;D;D;D
Polyphen		0.80	P;.;P;P;P
Vest4		0.25
MutPred		0.69		Loss of ubiquitination at K169 (P = 0.0877);.;Loss of ubiquitination at K169 (P = 0.0877);Loss of ubiquitination at K169 (P = 0.0877);Loss of ubiquitination at K169 (P = 0.0877);
MVP		0.36
MPC		0.15
ClinPred		0.15	T
GERP RS		-0.23
Varity_R		0.15
gMVP		0.28

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.

Other links and lift over

hg19: chr1-110464593;