NM_001040025.3:c.-3G>T

Variant names:

• chr17-81683756-C-A
• rs770789495
• NM_001040025.3:c.-3G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001040025.3(ARL16):​c.-3G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARL16 NM_001040025.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: BayesDel_addAF computational evidence supports a deleterious effect, 0.312

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040025.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL16	NM_001040025.3	MANE Select	c.-3G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001035114.2	B4E3H0
	ARL16	NM_001040025.3	MANE Select	c.-3G>T		5_prime_UTR	Exon 1 of 5	NP_001035114.2	B4E3H0
	ARL16	NM_001329608.2		c.-670G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_001316537.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL16	ENST00000622299.5	TSL:1 MANE Select	c.-3G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000483183.1	B4E3H0
	ARL16	ENST00000622299.5	TSL:1 MANE Select	c.-3G>T		5_prime_UTR	Exon 1 of 5	ENSP00000483183.1	B4E3H0
	HGS	ENST00000677161.1		c.-165+128C>A		intron	N/A	ENSP00000503695.1	A0A7I2V3Z1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	8.3
DANN	Uncertain	0.98
Eigen	Benign	0.18
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.27	N
PhyloP100		-0.69
Vest4		0.050
GERP RS		1.4
PromoterAI		-0.096	Neutral

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

Other links and lift over

dbSNP: rs770789495; hg19: chr17-79650786;