rs863223352

Positions:

• chr17-81683794-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The NM_001040025.3(ARL16):​c.-41G>T variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARL16 NM_001040025.3 5_prime_UTR
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.344

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]

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]

ARL16 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-81683794-C-A is Pathogenic according to our data. Variant chr17-81683794-C-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 208393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.08498457). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL16	NM_001040025.3	c.-41G>T		5_prime_UTR_variant	1/5	ENST00000622299.5	NP_001035114.2
ARL16	NM_001329608.2	c.-708G>T		5_prime_UTR_variant	1/5		NP_001316537.1
ARL16	NR_138058.2	n.4G>T		non_coding_transcript_exon_variant	1/6
ARL16	NM_001329609.2	c.-268G>T		upstream_gene_variant			NP_001316538.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL16	ENST00000622299.5	c.-41G>T		5_prime_UTR_variant	1/5	1	NM_001040025.3	ENSP00000483183.1
HGS	ENST00000677161.1	c.-165+166C>A		intron_variant				ENSP00000503695.1
ARL16	ENST00000577142.1	n.-13G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1452828 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723096

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Childhood-onset schizophrenia Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Dr. Guy Rouleau's laboratory, McGill University

Jan 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.9
DANN	Benign	0.64
DEOGEN2	Benign	0.0037	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.40	.;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.21	N;.
REVEL	Benign	0.15
Sift	Benign	0.063	T;.
Sift4G	Benign	0.26	T;T
Polyphen		0.023	B;B
Vest4		0.090
MutPred		0.54		Loss of methylation at R11 (P = 0.0012);Loss of methylation at R11 (P = 0.0012);
MVP		0.39
MPC		0.075
ClinPred		0.57	D
GERP RS		-7.8
Varity_R		0.068
gMVP		0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs863223352; hg19: chr17-79650824;