Variant chr4-73837255-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002993.4(CXCL6):c.295C>G(p.Leu99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000014 ( 0 hom. )

Consequence

CXCL6
NM_002993.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.640

Variant links:

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]

CXCL6 links:

CXCL6 (HGNC:):

CXCL6 links:

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ACMG classification

Classification made for transcript

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=0.08364099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL6	NM_002993.4 linkuse as main transcript	c.295C>G	p.Leu99Val	missense_variant	3/4	ENST00000226317.10	NP_002984.1	P80162

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CXCL6	ENST00000226317.10 linkuse as main transcript	c.295C>G	p.Leu99Val	missense_variant	3/4	1	NM_002993.4	ENSP00000226317.5	P80162
CXCL6	ENST00000515050.1 linkuse as main transcript	c.295C>G	p.Leu99Val	missense_variant	3/3	1		ENSP00000424819.1	D6RF92
CXCL6	ENST00000503446.1 linkuse as main transcript	n.69C>G		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2022

The c.295C>G (p.L99V) alteration is located in exon 3 (coding exon 3) of the CXCL6 gene. This alteration results from a C to G substitution at nucleotide position 295, causing the leucine (L) at amino acid position 99 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0060

DANN

Benign

0.076

DEOGEN2

Benign

0.042

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.084

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.085

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

1.2

N;N

REVEL

Benign

0.022

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.022

B;.

Vest4

0.29

MutPred

0.54

Gain of MoRF binding (P = 0.0889);Gain of MoRF binding (P = 0.0889);

MVP

0.11

MPC

0.30

ClinPred

0.052

GERP RS

-3.3

Varity_R

0.026

gMVP

0.16

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over