rs1314035658

Variant names:

• chr4-56523710-C-T
• rs1314035658
• NM_001363794.2:c.632C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001363794.2(ARL9):​c.632C>T​(p.Ala211Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ARL9 NM_001363794.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26
• Publications: 0 publications found

Genes affected

ARL9 (HGNC:23592): (ADP ribosylation factor like GTPase 9) ARL9 is a member of the small GTPase protein family with a high degree of similarity to ARF (MIM 103180) proteins of the RAS superfamily.[supplied by OMIM, Nov 2008]

ENSG00000289393 (HGNC:58796):

LOC105377665 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363794.2. 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
	ARL9	NM_001363794.2	MANE Select	c.632C>T	p.Ala211Val	missense	Exon 4 of 4	NP_001350723.1	A0A1W2PS79
	ARL9	NM_001401361.1		c.293C>T	p.Ala98Val	missense	Exon 2 of 2	NP_001388290.1
	ARL9	NM_001401357.1		c.206C>T	p.Ala69Val	missense	Exon 4 of 4	NP_001388286.1	Q6T311-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL9	ENST00000640821.3	TSL:5 MANE Select	c.632C>T	p.Ala211Val	missense	Exon 4 of 4	ENSP00000492671.3	A0A1W2PS79
	ARL9	ENST00000360096.3	TSL:1	c.206C>T	p.Ala69Val	missense	Exon 4 of 4	ENSP00000353210.2	Q6T311-2
	ARL9	ENST00000915214.1		c.548C>T	p.Ala183Val	missense	Exon 4 of 4	ENSP00000585273.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248206 AF XY: 0.00000743

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000274 AC: 4 AN: 1460634 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726586

African (AFR) AF: 0.0000598 AC: 2 AN: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111292

Other (OTH) AF: 0.0000166 AC: 1 AN: 60344

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74334

African (AFR) AF: 0.0000724 AC: 3 AN: 41444

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000354 Hom.: 0

Bravo AF: 0.0000113

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	0.58
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.27	D
PhyloP100		6.3
PrimateAI	Benign	0.46	T
REVEL	Uncertain	0.45
Sift4G	Uncertain	0.0040	D
Vest4		0.60
MVP		0.66
MPC		0.44
ClinPred		0.95	D
GERP RS		5.3
gMVP		0.47
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1314035658; hg19: chr4-57389876; COSMIC: COSV105921480;