Variant 17-4739365-G-C 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_001386809.1(CXCL16):c.-26C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

CXCL16
NM_001386809.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.23

Variant links:

Genes affected

CXCL16 (HGNC:16642): (C-X-C motif chemokine ligand 16) Enables chemokine activity. Involved in several processes, including positive regulation of cell growth; response to interferon-gamma; and response to tumor necrosis factor. Located in extracellular space. Biomarker of COVID-19 and systemic scleroderma. [provided by Alliance of Genome Resources, Apr 2022]

CXCL16 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=0.095853955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
CXCL16	NM_001386809.1 link	c.-26C>G	5_prime_UTR_premature_start_codon_gain_variant	1/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001386809.1 link	c.-26C>G	5_prime_UTR_variant	1/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2 link	c.-26C>G	5_prime_UTR_premature_start_codon_gain_variant	1/5		NP_001094282.2	Q9H2A7
CXCL16	NM_001100812.2 link	c.-26C>G	5_prime_UTR_variant	1/5		NP_001094282.2	Q9H2A7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CXCL16	ENST00000293778.12 link	c.-26C>G	5_prime_UTR_premature_start_codon_gain_variant	1/6	1	NM_001386809.1	ENSP00000293778.7	Q9H2A7
CXCL16	ENST00000574412.6 link	c.-26C>G	5_prime_UTR_premature_start_codon_gain_variant	1/5	1		ENSP00000459592.2	Q9H2A7
CXCL16	ENST00000293778.12 link	c.-26C>G	5_prime_UTR_variant	1/6	1	NM_001386809.1	ENSP00000293778.7	Q9H2A7
CXCL16	ENST00000574412.6 link	c.-26C>G	5_prime_UTR_variant	1/5	1		ENSP00000459592.2	Q9H2A7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247342

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134438

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

Dec 03, 2024

The c.32C>G (p.S11C) alteration is located in exon 1 (coding exon 1) of the CXCL16 gene. This alteration results from a C to G substitution at nucleotide position 32, causing the serine (S) at amino acid position 11 to be replaced by a cysteine (C). 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

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.89

DANN

Uncertain

0.98

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.034

M_CAP

Benign

0.0017

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.026

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.029

D;D

Vest4

0.12

MutPred

0.17

Loss of phosphorylation at S11 (P = 0.0041);Loss of phosphorylation at S11 (P = 0.0041);

MVP

0.22

MPC

0.66

ClinPred

0.57

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over