10-44373017-C-A

Variant names:

• chr10-44373017-C-A
• rs12258838
• ENST00000374429.6:c.*311G>T

Variant summary

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

The NM_001277990.2(CXCL12):​c.183G>T​(p.Leu61Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CXCL12 NM_001277990.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

Genes affected

CXCL12 (HGNC:10672): (C-X-C motif chemokine ligand 12) This antimicrobial gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

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=0.13959453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.183G>T	p.Leu61Phe	missense_variant	Exon 3 of 3		NP_001264919.1
CXCL12	NM_000609.7	c.*311G>T		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.*311G>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.183G>T	p.Leu61Phe	missense_variant	Exon 3 of 3	5		ENSP00000379139.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383730 Hom.: 0 Cov.: 34 AF XY: 0.00000146 AC XY: 1 AN XY: 682802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.22
DANN	Benign	0.71
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.26	.;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.83	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;.
Vest4		0.18
MutPred		0.19		Loss of glycosylation at S65 (P = 0.1748);Loss of glycosylation at S65 (P = 0.1748);
MVP		0.25
ClinPred		0.065	T
GERP RS		-2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12258838; hg19: chr10-44868465;