17-39156935-C-T

Position:

• chr17-39156935-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143968.1(ARL5C):​c.499G>A​(p.Ala167Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: ARL5C NM_001143968.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.04

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13563398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL5C	NM_001143968.1	c.499G>A	p.Ala167Thr	missense_variant	6/6	ENST00000269586.12
ARL5C	XM_047435964.1	c.*105-140G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL5C	ENST00000269586.12	c.499G>A	p.Ala167Thr	missense_variant	6/6	5	NM_001143968.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000195 AC: 3 AN: 154212 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399492 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690260

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000840

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.90	D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.15
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.012	D
Polyphen		0.041	B
Vest4		0.14
MutPred		0.53		Gain of disorder (P = 0.2752);
MVP		0.12
ClinPred		0.40	T
GERP RS		3.8
Varity_R		0.15
gMVP		0.085

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

LitVar

Other links and lift over

dbSNP: rs1376360578; hg19: chr17-37313188;