chr5-54171853-C-T

Variant names:

• chr5-54171853-C-T
• NM_019087.3:c.124G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_019087.3(ARL15):​c.124G>A​(p.Gly42Ser) 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: 7.88
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

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.124G>A	p.Gly42Ser	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.124G>A	p.Gly42Ser	missense	Exon 2 of 5	ENSP00000433427.1	Q9NXU5
	ARL15	ENST00000502271.5	TSL:1	c.-344-17214G>A		intron	N/A	ENSP00000473508.1	R4GN67
	ARL15	ENST00000505630.5	TSL:1	n.221G>A		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	Benign	0.22
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.6	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.029	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.88
MutPred		0.48		Gain of disorder (P = 0.0683)
MVP		0.91
MPC		0.88
ClinPred		0.86	D
GERP RS		5.9
Varity_R		0.34
gMVP		0.81
Mutation Taster		=21/79	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: chr5-53467683;