Variant 17-4735422-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001386809.1(CXCL16):c.388G>A(p.Ala130Thr) 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. 13/18 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: 7.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CXCL16
NM_001386809.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.593

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL16	NM_001386809.1 link	c.388G>A	p.Ala130Thr	missense_variant	4/6	ENST00000293778.12	NP_001373738.1
CXCL16	NM_001100812.2 link	c.388G>A	p.Ala130Thr	missense_variant	4/5		NP_001094282.2	Q9H2A7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL16	ENST00000293778.12 link	c.388G>A	p.Ala130Thr	missense_variant	4/6	1	NM_001386809.1	ENSP00000293778.7		Q9H2A7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000509

AC:

AN:

196554

Hom.:

AF XY:

0.00

AC XY:

AN XY:

103764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000375

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.23e-7

AC:

AN:

1382512

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000272

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000837

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

Jun 02, 2023

The c.445G>A (p.A149T) alteration is located in exon 4 (coding exon 4) of the CXCL16 gene. This alteration results from a G to A substitution at nucleotide position 445, causing the alanine (A) at amino acid position 149 to be replaced by a threonine (T). 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

-0.34

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.42

DANN

Benign

0.86

DEOGEN2

Benign

0.030

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.45

.;.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

N;.;.

REVEL

Benign

0.047

Sift

Benign

0.32

T;.;.

Sift4G

Benign

0.17

T;T;.

Vest4

0.040

MVP

0.092

MPC

0.17

ClinPred

0.047

GERP RS

-5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.080

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