Variant chr17-81683773-G-T 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_001040025.3(ARL16):c.-20C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,606,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ARL16
NM_001040025.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.159

Variant links:

Genes affected

ARL16 (HGNC:27902): (ADP ribosylation factor like GTPase 16) The protein encoded by this gene belongs to the ARL (ADP-ribosylation factor-like) family of proteins, which are structurally related to ADP-ribosylation factors (ARFs). This protein has been shown to have an inhibitory role in the cellular antiviral response. This gene product interacts with the C-terminal domain of the DEXD/H-box helicase 58 (DDX58) gene product. This interaction was found to suppress the association between the DDX58 gene product and RNA, thereby negatively regulating the activity of the DDX58 gene product. [provided by RefSeq, Jul 2016]

ARL16 links:

HGS (HGNC:4897): (hepatocyte growth factor-regulated tyrosine kinase substrate) The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation. [provided by RefSeq, Dec 2010]

HGS links:

Genome browser will be placed here

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=0.19944891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ARL16	NM_001040025.3 linkuse as main transcript	c.-20C>A	5_prime_UTR_variant	1/5	ENST00000622299.5
ARL16	NM_001329608.2 linkuse as main transcript	c.-687C>A	5_prime_UTR_variant	1/5
ARL16	NR_138058.2 linkuse as main transcript	n.25C>A	non_coding_transcript_exon_variant	1/6
ARL16	NM_001329609.2 linkuse as main transcript		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL16	ENST00000622299.5 linkuse as main transcript	c.-20C>A		5_prime_UTR_variant	1/5	1	NM_001040025.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1454354

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

723776

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:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000836

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

Aug 02, 2021

The c.53C>A (p.P18Q) alteration is located in exon 1 (coding exon 1) of the ARL16 gene. This alteration results from a C to A substitution at nucleotide position 53, causing the proline (P) at amino acid position 18 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.3

DANN

Benign

0.92

DEOGEN2

Benign

0.0032

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.28

.;T

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.020

N;.

REVEL

Benign

0.088

Sift

Uncertain

0.012

D;.

Sift4G

Benign

0.23

T;T

Polyphen

0.88

P;P

Vest4

0.13

MutPred

0.39

Gain of MoRF binding (P = 0.0249);Gain of MoRF binding (P = 0.0249);

MVP

0.58

MPC

0.063

ClinPred

0.16

GERP RS

0.37

Varity_R

0.075

gMVP

0.23

Splicing

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