rs786205563

Positions:

• chr3-94039955-T-A
• chr3-94039955-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_001174150.2(ARL13B):​c.765T>A​(p.Asn255Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL13B NM_001174150.2 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.120

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-94039955-T-A is Pathogenic according to our data. Variant chr3-94039955-T-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 191177.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL13B	NM_001174150.2	c.765T>A	p.Asn255Lys	missense_variant	6/10	ENST00000394222.8	NP_001167621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL13B	ENST00000394222.8	c.765T>A	p.Asn255Lys	missense_variant	6/10	1	NM_001174150.2	ENSP00000377769	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;.;T;T
Eigen	Benign	0.020
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.67	T;T;.;T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.3	.;.;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N;N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.010	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		1.0, 0.99	.;D;D;D
Vest4		0.74
MutPred		0.26		.;.;Gain of methylation at N255 (P = 0.0017);Gain of methylation at N255 (P = 0.0017);
MVP		0.69
MPC		0.31
ClinPred		0.97	D
GERP RS		0.50
Varity_R		0.17
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs786205563; hg19: chr3-93758799;