5-54113315-C-T

Variant names:

• chr5-54113315-C-T
• NM_019087.3:c.349G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019087.3(ARL15):​c.349G>A​(p.Glu117Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL15 NM_019087.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

ARL15 (HGNC:25945): (ADP ribosylation factor like GTPase 15) Predicted to enable GTP binding activity and GTPase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL15	NM_019087.3	c.349G>A	p.Glu117Lys	missense_variant	Exon 4 of 5	ENST00000504924.6	NP_061960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL15	ENST00000504924.6	c.349G>A	p.Glu117Lys	missense_variant	Exon 4 of 5	1	NM_019087.3	ENSP00000433427.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.349G>A (p.E117K) alteration is located in exon 4 (coding exon 4) of the ARL15 gene. This alteration results from a G to A substitution at nucleotide position 349, causing the glutamic acid (E) at amino acid position 117 to be replaced by a lysine (K). 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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.6	D;.;N
REVEL	Uncertain	0.31
Sift	Benign	0.15	T;.;T
Sift4G	Uncertain	0.057	T;T;T
Polyphen		0.82	P;.;.
Vest4		0.62
MutPred		0.41		Gain of ubiquitination at E117 (P = 0.0128);Gain of ubiquitination at E117 (P = 0.0128);Gain of ubiquitination at E117 (P = 0.0128);
MVP		0.71
MPC		0.33
ClinPred		0.95	D
GERP RS		5.9
Varity_R		0.52
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-53409145;