NM_001174150.2:c.1032T>C

Variant names:

• chr3-94049413-T-C
• rs561410801
• NM_001174150.2:c.1032T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001174150.2(ARL13B):​c.1032T>C​(p.Gly344Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,590,954 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000092 (3 hom.)
• Consequence: ARL13B NM_001174150.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.50
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 3-94049413-T-C is Benign according to our data. Variant chr3-94049413-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1169343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.5 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000592 (9/152064) while in subpopulation SAS AF = 0.00187 (9/4812). AF 95% confidence interval is 0.000975. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.1032T>C	p.Gly344Gly	synonymous	Exon 8 of 10	NP_001167621.1	Q3SXY8-1
	ARL13B	NM_182896.3		c.1032T>C	p.Gly344Gly	synonymous	Exon 8 of 11	NP_878899.1	Q3SXY8-1
	ARL13B	NM_001321328.2		c.987T>C	p.Gly329Gly	synonymous	Exon 9 of 11	NP_001308257.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL13B	ENST00000394222.8	TSL:1 MANE Select	c.1032T>C	p.Gly344Gly	synonymous	Exon 8 of 10	ENSP00000377769.3	Q3SXY8-1
	ARL13B	ENST00000471138.5	TSL:1	c.1032T>C	p.Gly344Gly	synonymous	Exon 8 of 11	ENSP00000420780.1	Q3SXY8-1
	ARL13B	ENST00000535334.5	TSL:1	c.723T>C	p.Gly241Gly	synonymous	Exon 7 of 9	ENSP00000445145.1	Q3SXY8-3

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000199 AC: 49 AN: 246004 AF XY: 0.000278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000917 AC: 132 AN: 1438890 Hom.: 3 Cov.: 27 AF XY: 0.000124 AC XY: 89 AN XY: 716538

African (AFR) AF: 0.00 AC: 0 AN: 32782

American (AMR) AF: 0.00 AC: 0 AN: 43742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39418

South Asian (SAS) AF: 0.00139 AC: 116 AN: 83454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00000822 AC: 9 AN: 1095310

Other (OTH) AF: 0.000101 AC: 6 AN: 59564

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41500

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000227

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Joubert syndrome 8 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.1
DANN	Benign	0.77
PhyloP100		1.5
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs561410801; hg19: chr3-93768257;