4-56523818-C-T

Variant names:

• chr4-56523818-C-T
• NM_001363794.2:c.740C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363794.2(ARL9):​c.740C>T​(p.Pro247Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P247R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL9 NM_001363794.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.53
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22070411).

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.740C>T	p.Pro247Leu	missense	Exon 4 of 4	NP_001350723.1	A0A1W2PS79
	ARL9	NM_001401361.1		c.401C>T	p.Pro134Leu	missense	Exon 2 of 2	NP_001388290.1
	ARL9	NM_001401357.1		c.314C>T	p.Pro105Leu	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.740C>T	p.Pro247Leu	missense	Exon 4 of 4	ENSP00000492671.3	A0A1W2PS79
	ARL9	ENST00000360096.3	TSL:1	c.314C>T	p.Pro105Leu	missense	Exon 4 of 4	ENSP00000353210.2	Q6T311-2
	ARL9	ENST00000915214.1		c.656C>T	p.Pro219Leu	missense	Exon 4 of 4	ENSP00000585273.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.16
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.87	T
PhyloP100		3.5
PrimateAI	Benign	0.44	T
REVEL	Benign	0.13
Sift4G	Benign	0.14	T
Vest4		0.22
MVP		0.18
MPC		0.44
ClinPred		0.95	D
GERP RS		5.3
gMVP		0.41
Mutation Taster		=80/20	polymorphism

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: chr4-57389984;