4-73836836-C-T

Position:

• chr4-73836836-C-T

Variant summary

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

The NM_002993.4(CXCL6):​c.86C>T​(p.Thr29Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CXCL6 NM_002993.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.485

Genes affected

CXCL6 (HGNC:10643): (C-X-C motif chemokine ligand 6) The protein encoded by this gene is a member CXC chemokine family. The encoded protein is a chemotactic for neutrophil granulocytes and has antibacterial action against gram-negative and gram-positive bacteria. This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, Jun 2020]

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=0.24437624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL6	NM_002993.4	c.86C>T	p.Thr29Met	missense_variant	1/4	ENST00000226317.10	NP_002984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL6	ENST00000226317.10	c.86C>T	p.Thr29Met	missense_variant	1/4	1	NM_002993.4	ENSP00000226317.5
CXCL6	ENST00000515050.1	c.86C>T	p.Thr29Met	missense_variant	1/3	1		ENSP00000424819.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460052 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726128

Gnomad4 AFR exome AF: 0.0000299

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.86C>T (p.T29M) alteration is located in exon 1 (coding exon 1) of the CXCL6 gene. This alteration results from a C to T substitution at nucleotide position 86, causing the threonine (T) at amino acid position 29 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	0.16
Eigen_PC	Benign	-0.013
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		1.0	D;.
Vest4		0.28
MutPred		0.24		Loss of glycosylation at T29 (P = 0.0097);Loss of glycosylation at T29 (P = 0.0097);
MVP		0.33
MPC		0.85
ClinPred		0.89	D
GERP RS		4.1
Varity_R		0.12
gMVP		0.47

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: rs1731113145; hg19: chr4-74702553;