Variant 7-12688687-T-C 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_005738.5(ARL4A):c.433T>C(p.Ser145Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ARL4A
NM_005738.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.494

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08777535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARL4A	NM_005738.5 linkuse as main transcript	c.433T>C	p.Ser145Pro	missense_variant	2/2	ENST00000651779.1	NP_005729.1
ARL4A	NM_001037164.3 linkuse as main transcript	c.433T>C	p.Ser145Pro	missense_variant	2/2		NP_001032241.1
ARL4A	NM_001195396.2 linkuse as main transcript	c.433T>C	p.Ser145Pro	missense_variant	2/2		NP_001182325.1
ARL4A	NM_212460.4 linkuse as main transcript	c.433T>C	p.Ser145Pro	missense_variant	2/2		NP_997625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL4A	ENST00000651779.1 linkuse as main transcript	c.433T>C	p.Ser145Pro	missense_variant	2/2		NM_005738.5	ENSP00000498350	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251144

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135730

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727134

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 06, 2022

The c.433T>C (p.S145P) alteration is located in exon 2 (coding exon 1) of the ARL4A gene. This alteration results from a T to C substitution at nucleotide position 433, causing the serine (S) at amino acid position 145 to be replaced by a proline (P). 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

0.071

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

T;T;T;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.75

.;.;.;T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.088

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;L;L;L;L

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.3

N;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.042

D;D;D;D;D

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.015

B;B;B;B;B

Vest4

0.058

MutPred

0.45

Loss of phosphorylation at S145 (P = 0.0368);Loss of phosphorylation at S145 (P = 0.0368);Loss of phosphorylation at S145 (P = 0.0368);Loss of phosphorylation at S145 (P = 0.0368);Loss of phosphorylation at S145 (P = 0.0368);

MVP

0.74

MPC

0.80

ClinPred

0.23

GERP RS

-1.3

Varity_R

0.65

gMVP

0.63

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