3-94019850-A-G

Position:

• chr3-94019850-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001174150.2(ARL13B):​c.381-15481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,068 control chromosomes in the GnomAD database, including 842 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (842 hom., cov: 32)
• Consequence: ARL13B NM_001174150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151

Genes affected

STX19 (HGNC:19300): (syntaxin 19) Predicted to enable SNAP receptor activity and SNARE binding activity. Predicted to be involved in intracellular protein transport; synaptic vesicle fusion to presynaptic active zone membrane; and vesicle docking. Predicted to be part of SNARE complex. Predicted to be active in presynaptic active zone membrane and synaptic vesicle. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX19	NM_001001850.3	c.-13-4568T>C		intron_variant		ENST00000315099.3	NP_001001850.1
ARL13B	NM_001174150.2	c.381-15481A>G		intron_variant		ENST00000394222.8	NP_001167621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX19	ENST00000315099.3	c.-13-4568T>C		intron_variant		1	NM_001001850.3	ENSP00000320679	P1
ARL13B	ENST00000394222.8	c.381-15481A>G		intron_variant		1	NM_001174150.2	ENSP00000377769	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15845 AN: 151950 Hom.: 843 Cov.: 32

Gnomad AFR AF: 0.0959

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0985

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 15840 AN: 152068 Hom.: 842 Cov.: 32 AF XY: 0.103 AC XY: 7661 AN XY: 74320

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.0849

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0985

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.113

Alfa AF: 0.116 Hom.: 1406

Bravo AF: 0.101

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.71
DANN	Benign	0.47

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: rs13071953; hg19: chr3-93738694;