Variant 7-12688292-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005738.5(ARL4A):c.38C>G(p.Ser13Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000023 in 1,611,532 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

ARL4A
NM_005738.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

Variant links:

Genes affected

ARL4A (HGNC:695): (ADP ribosylation factor like GTPase 4A) ADP-ribosylation factor-like 4A is a member of the ADP-ribosylation factor family of GTP-binding proteins. ARL4A is similar to ARL4C and ARL4D and each has a nuclear localization signal and an unusually high guaninine nucleotide exchange rate. ARL4A is located in both the nuclear and extranuclear cell compartments. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ARL4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36934197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL4A	NM_005738.5 linkuse as main transcript	c.38C>G	p.Ser13Cys	missense_variant	2/2	ENST00000651779.1	NP_005729.1	P40617A0A024R9Z2
ARL4A	NM_001037164.3 linkuse as main transcript	c.38C>G	p.Ser13Cys	missense_variant	2/2		NP_001032241.1	P40617A0A024R9Z2
ARL4A	NM_001195396.2 linkuse as main transcript	c.38C>G	p.Ser13Cys	missense_variant	2/2		NP_001182325.1	P40617A0A024R9Z2
ARL4A	NM_212460.4 linkuse as main transcript	c.38C>G	p.Ser13Cys	missense_variant	2/2		NP_997625.1	P40617A0A024R9Z2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL4A	ENST00000651779.1 linkuse as main transcript	c.38C>G	p.Ser13Cys	missense_variant	2/2		NM_005738.5	ENSP00000498350.1		P40617

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

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:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000482

AC:

AN:

249142

Hom.:

AF XY:

0.0000818

AC XY:

AN XY:

134520

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:

0.000364

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1459350

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

725674

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:

0.000385

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

May 12, 2024

The c.38C>G (p.S13C) alteration is located in exon 2 (coding exon 1) of the ARL4A gene. This alteration results from a C to G substitution at nucleotide position 38, causing the serine (S) at amino acid position 13 to be replaced by a cysteine (C). 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

Benign

0.099

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

T;T;T;.;T;T

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;.;.;D;D;.

M_CAP

Benign

0.027

MetaRNN

Benign

0.37

T;T;T;T;T;T

MetaSVM

Uncertain

0.0021

MutationAssessor

Uncertain

2.4

M;M;M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.4

D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Uncertain

0.041

D;D;D;D;D;D

Polyphen

1.0

D;D;D;.;D;D

Vest4

0.38

MVP

0.52

MPC

1.3

ClinPred

0.49

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.37

gMVP

0.50

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

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