3-93980478-G-A

Position:

• chr3-93980478-G-A

Variant summary

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

The NM_001174150.2(ARL13B):​c.55G>A​(p.Val19Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL13B NM_001174150.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

Genes affected

ARL13B (HGNC:25419): (ADP ribosylation factor like GTPase 13B) This gene encodes a member of the ADP-ribosylation factor-like family. The encoded protein is a small GTPase that contains both N-terminal and C-terminal guanine nucleotide-binding motifs. This protein is localized in the cilia and plays a role in cilia formation and in maintenance of cilia. Mutations in this gene are the cause of Joubert syndrome 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

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=0.17351541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL13B	NM_001174150.2	c.55G>A	p.Val19Ile	missense_variant	1/10	ENST00000394222.8	NP_001167621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL13B	ENST00000394222.8	c.55G>A	p.Val19Ile	missense_variant	1/10	1	NM_001174150.2	ENSP00000377769	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2023

The c.55G>A (p.V19I) alteration is located in exon 1 (coding exon 1) of the ARL13B gene. This alteration results from a G to A substitution at nucleotide position 55, causing the valine (V) at amino acid position 19 to be replaced by an isoleucine (I). 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	0.079
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.041	.;T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.38	T;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	N;N;N
MutationTaster	Benign	0.93	D;D;D;D;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.23	N;N;N
REVEL	Benign	0.053
Sift	Benign	0.11	T;T;T
Sift4G	Uncertain	0.035	D;T;T
Polyphen		0.15	B;B;B
Vest4		0.34
MutPred		0.35		Gain of catalytic residue at L24 (P = 0.0458);Gain of catalytic residue at L24 (P = 0.0458);Gain of catalytic residue at L24 (P = 0.0458);
MVP		0.37
MPC		0.062
ClinPred		0.14	T
GERP RS		4.2
Varity_R		0.063
gMVP		0.23

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: chr3-93699322;