rs1390167347

Variant names:

• chr3-94049439-T-A
• NM_001174150.2:c.1058T>A

Your query was ambiguous. Multiple possible variants found:

• chr3-94049439-T-A
• chr3-94049439-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001174150.2(ARL13B):​c.1058T>A​(p.Met353Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M353T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ARL13B NM_001174150.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2703493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARL13B	NM_001174150.2	c.1058T>A	p.Met353Lys	missense_variant	Exon 8 of 10	ENST00000394222.8	NP_001167621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARL13B	ENST00000394222.8	c.1058T>A	p.Met353Lys	missense_variant	Exon 8 of 10	1	NM_001174150.2	ENSP00000377769.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457204 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724628

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.062	.;.;T;T
Eigen	Benign	0.031
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T;T;.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.69	.;.;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.2	N;N;N;N
REVEL	Benign	0.074
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.26, 0.017	.;B;B;B
Vest4		0.44
MutPred		0.30		.;.;Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);
MVP		0.59
MPC		0.13
ClinPred		0.73	D
GERP RS		5.1
Varity_R		0.76
gMVP		0.35

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: chr3-93768283;