5-132060983-A-T

Variant names:

• chr5-132060983-A-T
• rs35482671
• NM_000588.4:c.179A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000588.4(IL3):​c.179A>T​(p.Asn60Ile) 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. 14/22 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. N60S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL3 NM_000588.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 0 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]

ENSG00000303119 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20272303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL3	NM_000588.4	c.179A>T	p.Asn60Ile	missense_variant	Exon 2 of 5	ENST00000296870.3	NP_000579.2
LOC105379174	XR_001742531.2	n.211+488T>A		intron_variant	Intron 2 of 4
LOC105379174	XR_948784.3	n.398+488T>A		intron_variant	Intron 2 of 2
LOC105379174	XR_948785.3	n.228+488T>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL3	ENST00000296870.3	c.179A>T	p.Asn60Ile	missense_variant	Exon 2 of 5	1	NM_000588.4	ENSP00000296870.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.8
DANN	Benign	0.96
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		-1.2
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.042
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.020	D
Polyphen		0.35	B
Vest4		0.20
MutPred		0.56		Loss of disorder (P = 0.0194);
MVP		0.32
MPC		0.83
ClinPred		0.84	D
GERP RS		-5.8
PromoterAI		0.016	Neutral
Varity_R		0.36
gMVP		0.68
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: rs35482671; hg19: chr5-131396676;