5-54171882-T-A

Variant names:

• chr5-54171882-T-A
• NM_019087.3:c.95A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019087.3. 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
	ARL15	NM_019087.3	MANE Select	c.95A>T	p.Glu32Val	missense	Exon 2 of 5	NP_061960.1	Q9NXU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL15	ENST00000504924.6	TSL:1 MANE Select	c.95A>T	p.Glu32Val	missense	Exon 2 of 5	ENSP00000433427.1	Q9NXU5
	ARL15	ENST00000502271.5	TSL:1	c.-344-17243A>T		intron	N/A	ENSP00000473508.1	R4GN67
	ARL15	ENST00000505630.5	TSL:1	n.192A>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.056	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		8.0
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.4	D
REVEL	Pathogenic	0.66
Sift	Benign	0.046	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.89	P
Vest4		0.88
MutPred		0.64		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
Mutation Taster		=32/68	disease causing

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

hg19: chr5-53467712;