17-36089253-G-C

Variant names:

• chr17-36089253-G-C
• rs764705131
• NM_002983.3:c.118C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_002983.3(CCL3):​c.118C>G​(p.Arg40Gly) 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. 11/18 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. R40W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCL3 NM_002983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a mutagenesis_site Slightly reduces heparin binding. (size 0) in uniprot entity CCL3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41737407).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002983.3. 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
	CCL3	NM_002983.3	MANE Select	c.118C>G	p.Arg40Gly	missense	Exon 2 of 3	NP_002974.1	P10147
	CCL3	NR_168494.1		n.891C>G		non_coding_transcript_exon	Exon 1 of 2
	CCL3	NR_168495.1		n.101C>G		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL3	ENST00000613922.2	TSL:1 MANE Select	c.118C>G	p.Arg40Gly	missense	Exon 2 of 3	ENSP00000477908.1	P10147
	CCL3	ENST00000614051.1	TSL:1	n.917C>G		non_coding_transcript_exon	Exon 1 of 2
	CCL3	ENST00000613928.1	TSL:5	n.803+79C>G		intron	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	Uncertain	0.39
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.012
PrimateAI	Benign	0.24	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.94	P
Vest4		0.42
MutPred		0.56		Loss of solvent accessibility (P = 0.0159)
MVP		0.40
ClinPred		0.75	D
GERP RS		-0.46
Varity_R		0.57
gMVP		0.55

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: rs764705131; hg19: chr17-34416599;