5-176365588-T-G

Position:

• chr5-176365588-T-G

Variant summary

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

The NM_173664.6(ARL10):​c.25T>G​(p.Leu9Val) 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 benign outcome for this variant. 14/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARL10 NM_173664.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.953

Genes affected

ARL10 (HGNC:22042): (ADP ribosylation factor like GTPase 10) Predicted to enable GTP binding activity and GTPase activity. [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=0.14645961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL10	NM_173664.6	c.25T>G	p.Leu9Val	missense_variant	1/4	ENST00000310389.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL10	ENST00000310389.6	c.25T>G	p.Leu9Val	missense_variant	1/4	2	NM_173664.6	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1092228 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 519054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Dec 01, 2022

The c.25T>G (p.L9V) alteration is located in exon 1 (coding exon 1) of the ARL10 gene. This alteration results from a T to G substitution at nucleotide position 25, causing the leucine (L) at amino acid position 9 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	Benign	0.090
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.70
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	0.92	N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.090	N
REVEL	Benign	0.093
Sift	Benign	0.16	T
Sift4G	Benign	0.28	T
Polyphen		0.010	B
Vest4		0.21
MutPred		0.17		Loss of glycosylation at P8 (P = 0.147);
MVP		0.50
MPC		1.9
ClinPred		0.22	T
GERP RS		-0.72
Varity_R		0.056
gMVP		0.53

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: chr5-175792591;