3-5178703-G-T

Variant names:

• chr3-5178703-G-T
• NM_018184.3:c.551G>T

Variant summary

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

The NM_018184.3(ARL8B):​c.551G>T​(p.Arg184Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: ARL8B NM_018184.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.63
• Publications: 0 publications found

Genes affected

ARL8B (HGNC:25564): (ADP ribosylation factor like GTPase 8B) Enables guanyl ribonucleotide binding activity and tubulin binding activity. Involved in several processes, including calcium ion regulated lysosome exocytosis; lysosomal transport; and vesicle fusion. Located in cytolytic granule membrane; midbody; and spindle midzone. Colocalizes with lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000233912 (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_018184.3. 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
	ARL8B	NM_018184.3	MANE Select	c.551G>T	p.Arg184Ile	missense	Exon 7 of 7	NP_060654.1	Q9NVJ2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL8B	ENST00000256496.8	TSL:1 MANE Select	c.551G>T	p.Arg184Ile	missense	Exon 7 of 7	ENSP00000256496.3	Q9NVJ2-1
	ARL8B	ENST00000419534.2	TSL:2	c.412G>T	p.Glu138*	stop_gained	Exon 5 of 5	ENSP00000402996.2	Q9NVJ2-2
	ARL8B	ENST00000967326.1		c.389G>T	p.Arg130Ile	missense	Exon 5 of 5	ENSP00000637385.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459442 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726174

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110868

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 33

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	0.29
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		9.6
Vest4		0.16
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.27
Mutation Taster		=51/149	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr3-5220388;