17-36089282-G-C

Variant names:

• chr17-36089282-G-C
• rs368462880
• NM_002983.3:c.89C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002983.3(CCL3):​c.89C>G​(p.Pro30Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCL3 NM_002983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

Genes affected

CCL3 (HGNC:10627): (C-C motif chemokine ligand 3) This locus represents a small inducible cytokine. The encoded protein, also known as macrophage inflammatory protein 1 alpha, plays a role in inflammatory responses through binding to the receptors CCR1, CCR4 and CCR5. Polymorphisms at this locus may be associated with both resistance and susceptibility to infection by human immunodeficiency virus type 1.[provided by RefSeq, Sep 2010]

CCL3-AS1 (HGNC:55229): (CCL3 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL3	NM_002983.3	c.89C>G	p.Pro30Arg	missense_variant	Exon 2 of 3	ENST00000613922.2	NP_002974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL3	ENST00000613922.2	c.89C>G	p.Pro30Arg	missense_variant	Exon 2 of 3	1	NM_002983.3	ENSP00000477908.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251236 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.45	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.60		Gain of methylation at P30 (P = 0.0636);
MVP		0.59
ClinPred		0.84	D
GERP RS		4.3
Varity_R		0.62
gMVP		0.52

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

LitVar

Other links and lift over

dbSNP: rs368462880; hg19: chr17-34416628;