3-94049503-A-C

Position:

• chr3-94049503-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001174150.2(ARL13B):​c.1122A>C​(p.Pro374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00098 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARL13B NM_001174150.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-94049503-A-C is Benign according to our data. Variant chr3-94049503-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3341728.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-94049503-A-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=1.48 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL13B	NM_001174150.2	c.1122A>C	p.Pro374=	synonymous_variant	8/10	ENST00000394222.8	NP_001167621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL13B	ENST00000394222.8	c.1122A>C	p.Pro374=	synonymous_variant	8/10	1	NM_001174150.2	ENSP00000377769	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 31 AN: 143856 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000765

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000429

Gnomad ASJ AF: 0.000594

Gnomad EAS AF: 0.000862

Gnomad SAS AF: 0.00139

Gnomad FIN AF: 0.000435

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000758

Gnomad OTH AF: 0.000509

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000977 AC: 1145 AN: 1171806 Hom.: 0 Cov.: 28 AF XY: 0.000968 AC XY: 572 AN XY: 591028

Gnomad4 AFR exome AF: 0.000853

Gnomad4 AMR exome AF: 0.0000959

Gnomad4 ASJ exome AF: 0.000833

Gnomad4 EAS exome AF: 0.00104

Gnomad4 SAS exome AF: 0.000298

Gnomad4 FIN exome AF: 0.000962

Gnomad4 NFE exome AF: 0.00109

Gnomad4 OTH exome AF: 0.000989

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000215 AC: 31 AN: 143992 Hom.: 0 Cov.: 31 AF XY: 0.000272 AC XY: 19 AN XY: 69792

Gnomad4 AFR AF: 0.0000762

Gnomad4 AMR AF: 0.000428

Gnomad4 ASJ AF: 0.000594

Gnomad4 EAS AF: 0.000864

Gnomad4 SAS AF: 0.00139

Gnomad4 FIN AF: 0.000435

Gnomad4 NFE AF: 0.0000758

Gnomad4 OTH AF: 0.000503

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

ARL13B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.1
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2077035252; hg19: chr3-93768347;