17-39161299-C-G

Variant names:

• chr17-39161299-C-G
• rs767380922
• NM_001143968.1:c.308G>C

Variant summary

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

The NM_001143968.1(ARL5C):​c.308G>C​(p.Arg103Pro) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R103Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL5C NM_001143968.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 2 publications found

Genes affected

ARL5C (HGNC:31111): (ADP ribosylation factor like GTPase 5C) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport; protein localization to Golgi membrane; and vesicle-mediated transport. Predicted to be active in trans-Golgi network. [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_001143968.1. 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
	ARL5C	NM_001143968.1	MANE Select	c.308G>C	p.Arg103Pro	missense	Exon 4 of 6	NP_001137440.1	A6NH57

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL5C	ENST00000269586.12	TSL:5 MANE Select	c.308G>C	p.Arg103Pro	missense	Exon 4 of 6	ENSP00000269586.7	A6NH57
	ARL5C	ENST00000578912.1	TSL:4	n.77G>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000466347.1	K7EM39

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		1.4
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.69		Loss of helix (P = 0.028)
MVP		0.24
ClinPred		0.99	D
GERP RS		-0.56
Varity_R		0.82
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs767380922; hg19: chr17-37317552;