chr3-94049389-T-A

Variant names:

• chr3-94049389-T-A
• rs1286731987
• NM_001174150.2:c.1025-17T>A

Variant summary

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

The NM_001174150.2(ARL13B):​c.1025-17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,330,274 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: ARL13B NM_001174150.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 0 publications found

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]

DHFR2 (HGNC:27309): (dihydrofolate reductase 2) Enables dihydrofolate reductase activity and mRNA binding activity. Involved in tetrahydrofolate metabolic process and thymidine biosynthetic process. Located in mitochondrial inner membrane and mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

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_001174150.2. 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
	ARL13B	NM_001174150.2	MANE Select	c.1025-17T>A		intron	N/A	NP_001167621.1	Q3SXY8-1
	ARL13B	NM_182896.3		c.1025-17T>A		intron	N/A	NP_878899.1	Q3SXY8-1
	ARL13B	NM_001321328.2		c.980-17T>A		intron	N/A	NP_001308257.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL13B	ENST00000394222.8	TSL:1 MANE Select	c.1025-17T>A		intron	N/A	ENSP00000377769.3	Q3SXY8-1
	ARL13B	ENST00000471138.5	TSL:1	c.1025-17T>A		intron	N/A	ENSP00000420780.1	Q3SXY8-1
	ARL13B	ENST00000535334.5	TSL:1	c.716-17T>A		intron	N/A	ENSP00000445145.1	Q3SXY8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1330274 Hom.: 0 Cov.: 19 AF XY: 0.00000150 AC XY: 1 AN XY: 667926

African (AFR) AF: 0.00 AC: 0 AN: 30270

American (AMR) AF: 0.00 AC: 0 AN: 42282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24906

East Asian (EAS) AF: 0.00 AC: 0 AN: 38860

South Asian (SAS) AF: 0.00 AC: 0 AN: 79466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5464

European-Non Finnish (NFE) AF: 0.00000100 AC: 1 AN: 1000342

Other (OTH) AF: 0.00 AC: 0 AN: 55762

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Benign	0.65
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.47		Position offset: -30
DS_AL_spliceai		0.47		Position offset: 17

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1286731987; hg19: chr3-93768233;