chrX-100985885-G-C

Position:

• chrX-100985885-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001162491.2(ARL13A):​c.349G>C​(p.Asp117His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,094,395 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ARL13A NM_001162491.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.15

Genes affected

ARL13A (HGNC:31709): (ADP ribosylation factor like GTPase 13A) Predicted to enable GTP binding activity and GTPase activity. Predicted to be involved in non-motile cilium assembly and receptor localization to non-motile cilium. Predicted to be active in ciliary membrane; motile cilium; and non-motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

TRMT2B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19231546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL13A	NM_001162491.2	c.349G>C	p.Asp117His	missense_variant	4/8	ENST00000450049.7	NP_001155963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL13A	ENST00000450049.7	c.349G>C	p.Asp117His	missense_variant	4/8	5	NM_001162491.2	ENSP00000398637	P1
ARL13A	ENST00000450457.6	c.349G>C	p.Asp117His	missense_variant, NMD_transcript_variant	4/9	2		ENSP00000414757

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094395 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 360007

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Leipzig Medical Center

Jan 01, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.27
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.70	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.082
Sift	Benign	0.75	T
Sift4G	Benign	0.55	T
Vest4		0.17
MutPred		0.53		Loss of stability (P = 0.0311);
MVP		0.78
MPC		0.31
ClinPred		0.73	D
GERP RS		4.4
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs373334251; hg19: chrX-100240874;