chr17-46517231-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000445552.6(ARL17A):ā€‹c.262C>Gā€‹(p.Leu88Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00010 ( 2 hom., cov: 14)
Exomes š‘“: 0.0000042 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

ARL17A
ENST00000445552.6 missense, splice_region

Scores

3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.646
Variant links:
Genes affected
ARL17A (HGNC:24096): (ADP ribosylation factor like GTPase 17A) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04620132).
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRC37A2NM_001006607.3 linkuse as main transcriptc.2610-131G>C intron_variant ENST00000576629.6 NP_001006608.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRC37A2ENST00000576629.6 linkuse as main transcriptc.2610-131G>C intron_variant 5 NM_001006607.3 ENSP00000459551 P1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
9
AN:
85942
Hom.:
2
Cov.:
14
show subpopulations
Gnomad AFR
AF:
0.000284
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000415
AC:
5
AN:
120428
Hom.:
1
AF XY:
0.00
AC XY:
0
AN XY:
63548
show subpopulations
Gnomad AFR exome
AF:
0.000447
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000425
AC:
3
AN:
706516
Hom.:
1
Cov.:
4
AF XY:
0.00000288
AC XY:
1
AN XY:
347664
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000654
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:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000105
AC:
9
AN:
85942
Hom.:
2
Cov.:
14
AF XY:
0.0000236
AC XY:
1
AN XY:
42362
show subpopulations
Gnomad4 AFR
AF:
0.000284
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000597
AC:
4

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 submitterclinical testingAmbry GeneticsJul 21, 2021The c.262C>G (p.L88V) alteration is located in exon 4 (coding exon 3) of the ARL17A gene. This alteration results from a C to G substitution at nucleotide position 262, causing the leucine (L) at amino acid position 88 to be replaced by a valine (V). 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
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
17
DANN
Benign
0.92
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.048
N
M_CAP
Uncertain
0.17
D
MetaRNN
Benign
0.046
T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N;N;N;N;N
PROVEAN
Benign
0.040
N
REVEL
Benign
0.045
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0020
D
Vest4
0.33
MVP
0.081
ClinPred
0.041
T
GERP RS
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs774773833; hg19: chr17-44594597; API