3-94049410-T-G

Variant names:

• chr3-94049410-T-G
• NM_001174150.2:c.1029T>G
• ARL13B p.Asn343Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001174150.2(ARL13B):​c.1029T>G​(p.Asn343Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N343N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARL13B NM_001174150.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13672563).

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.1029T>G	p.Asn343Lys	missense	Exon 8 of 10	NP_001167621.1	Q3SXY8-1
	ARL13B	NM_182896.3		c.1029T>G	p.Asn343Lys	missense	Exon 8 of 11	NP_878899.1	Q3SXY8-1
	ARL13B	NM_001321328.2		c.984T>G	p.Asn328Lys	missense	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.1029T>G	p.Asn343Lys	missense	Exon 8 of 10	ENSP00000377769.3	Q3SXY8-1
	ARL13B	ENST00000471138.5	TSL:1	c.1029T>G	p.Asn343Lys	missense	Exon 8 of 11	ENSP00000420780.1	Q3SXY8-1
	ARL13B	ENST00000535334.5	TSL:1	c.720T>G	p.Asn240Lys	missense	Exon 7 of 9	ENSP00000445145.1	Q3SXY8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.1
DANN	Benign	0.94
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.58
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.031
Sift	Uncertain	0.022	D
Sift4G	Benign	0.79	T
Varity_R		0.070
gMVP		0.12
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-93768254;