rs780057953

Variant names:

• chr5-132062766-C-A
• rs780057953
• NM_000588.4:c.434C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132062766-C-A
• chr5-132062766-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000588.4(IL3):​c.434C>A​(p.Thr145Lys) 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. 16/22 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. T145M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL3 NM_000588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 3 publications found

Genes affected

IL3 (HGNC:6011): (interleukin 3) The protein encoded by this gene is a potent growth promoting cytokine. This cytokine is capable of supporting the proliferation of a broad range of hematopoietic cell types. It is involved in a variety of cell activities such as cell growth, differentiation and apoptosis. This cytokine has been shown to also possess neurotrophic activity, and it may be associated with neurologic disorders. [provided by RefSeq, Jul 2008]

LOC105379174 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04591185).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000588.4. 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
	IL3	NM_000588.4	MANE Select	c.434C>A	p.Thr145Lys	missense	Exon 5 of 5	NP_000579.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL3	ENST00000296870.3	TSL:1 MANE Select	c.434C>A	p.Thr145Lys	missense	Exon 5 of 5	ENSP00000296870.2	P08700
	ENSG00000303119	ENST00000791953.1		n.-42G>T		upstream_gene	N/A
	ENSG00000303119	ENST00000791954.1		n.-17G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.35
DANN	Benign	0.40
DEOGEN2	Benign	0.24	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.00082	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.82
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.38	N
REVEL	Benign	0.0010
Sift	Benign	0.058	T
Polyphen		0.0050	B
Vest4		0.12
MutPred		0.25		Gain of ubiquitination at T145 (P = 0.0131)
MVP		0.14
MPC		0.27
ClinPred		0.14	T
GERP RS		-7.7
Varity_R		0.045
gMVP		0.19
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs780057953; hg19: chr5-131398459;