Variant 5-176371738-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173664.6(ARL10):c.578T>G(p.Met193Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARL10
NM_173664.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

ARL10 (HGNC:22042): (ADP ribosylation factor like GTPase 10) Predicted to enable GTP binding activity and GTPase activity. [provided by Alliance of Genome Resources, Apr 2022]

ARL10 links:

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ACMG classification

Classification made for transcript

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=0.20636317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL10	NM_173664.6 linkuse as main transcript	c.578T>G	p.Met193Arg	missense_variant	4/4	ENST00000310389.6	NP_775935.1	Q8N8L6Q6PCE2
ARL10	XM_011534529.4 linkuse as main transcript	c.561+2756T>G		intron_variant			XP_011532831.1
ARL10	XM_011534530.4 linkuse as main transcript	c.561+2756T>G		intron_variant			XP_011532832.1
ARL10	XM_011534531.4 linkuse as main transcript	c.562-484T>G		intron_variant			XP_011532833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARL10	ENST00000310389.6 linkuse as main transcript	c.578T>G	p.Met193Arg	missense_variant	4/4	2	NM_173664.6	ENSP00000308496.5	Q8N8L6
ARL10	ENST00000503175.1 linkuse as main transcript	c.36+2756T>G		intron_variant		3		ENSP00000424831.1	H0Y9R6
ARL10	ENST00000514533.1 linkuse as main transcript	c.132+2756T>G		intron_variant		3		ENSP00000421449.1	H0Y8L6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251170

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135752

show subpopulations

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 SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.578T>G (p.M193R) alteration is located in exon 4 (coding exon 4) of the ARL10 gene. This alteration results from a T to G substitution at nucleotide position 578, causing the methionine (M) at amino acid position 193 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.049

Eigen

Benign

-0.11

Eigen_PC

Benign

0.084

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.61

M_CAP

Benign

0.026

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.18

Sift

Benign

0.18

Sift4G

Benign

0.25

Polyphen

0.0030

Vest4

0.40

MutPred

0.58

Gain of helix (P = 0.0496);

MVP

0.79

MPC

0.71

ClinPred

0.43

GERP RS

5.4

Varity_R

0.54

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over