chr5-54171882-T-A

Position:

• chr5-54171882-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_019087.3(ARL15):​c.95A>T​(p.Glu32Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL15 NM_019087.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.98

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL15	NM_019087.3	c.95A>T	p.Glu32Val	missense_variant	2/5	ENST00000504924.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL15	ENST00000504924.6	c.95A>T	p.Glu32Val	missense_variant	2/5	1	NM_019087.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.95A>T (p.E32V) alteration is located in exon 2 (coding exon 2) of the ARL15 gene. This alteration results from a A to T substitution at nucleotide position 95, causing the glutamic acid (E) at amino acid position 32 to be replaced by a valine (V). 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	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;.
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	-0.056	T
MutationAssessor	Pathogenic	3.0	M;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.4	D;.;D
REVEL	Pathogenic	0.66
Sift	Benign	0.046	D;.;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.89	P;.;.
Vest4		0.88
MutPred		0.64		Loss of catalytic residue at E32 (P = 0.0348);Loss of catalytic residue at E32 (P = 0.0348);Loss of catalytic residue at E32 (P = 0.0348);
MVP		0.82
MPC		0.86
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.41
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-53467712;