Variant 17-39161326-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_001143968.1(ARL5C):c.281C>T(p.Thr94Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000047 in 1,551,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ARL5C
NM_001143968.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

ARL5C (HGNC:31111): (ADP ribosylation factor like GTPase 5C) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport; protein localization to Golgi membrane; and vesicle-mediated transport. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ARL5C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37569326).

BP6

Variant 17-39161326-G-A is Benign according to our data. Variant chr17-39161326-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3129564.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARL5C	NM_001143968.1 linkuse as main transcript	c.281C>T	p.Thr94Met	missense_variant	4/6	ENST00000269586.12	NP_001137440.1
ARL5C	XM_047435964.1 linkuse as main transcript	c.281C>T	p.Thr94Met	missense_variant	4/6		XP_047291920.1
ARL5C	XM_047435963.1 linkuse as main transcript	c.152C>T	p.Thr51Met	missense_variant	3/4		XP_047291919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL5C	ENST00000269586.12 linkuse as main transcript	c.281C>T	p.Thr94Met	missense_variant	4/6	5	NM_001143968.1	ENSP00000269586	P1
ARL5C	ENST00000578912.1 linkuse as main transcript	c.50C>T	p.Thr17Met	missense_variant, NMD_transcript_variant	2/4	4		ENSP00000466347

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000572

AC:

AN:

157318

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83256

show subpopulations

Gnomad AFR exome

AF:

0.000622

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000422

AC:

AN:

1399656

Hom.:

Cov.:

AF XY:

0.0000362

AC XY:

AN XY:

690328

show subpopulations

Gnomad4 AFR exome

AF:

0.000348

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.000199

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.0000361

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000764

Hom.:

Bravo

AF:

0.000136

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000378

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.12

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.79

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.77

M_CAP

Benign

0.076

MetaRNN

Benign

0.38

MetaSVM

Uncertain

0.30

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.39

Sift

Uncertain

0.014

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.28

MVP

0.26

ClinPred

0.72

GERP RS

0.63

Varity_R

0.41

gMVP

0.31

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