13-106559541-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018011.4(ARGLU1):​c.464G>A​(p.Arg155Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ARGLU1
NM_018011.4 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46
Variant links:
Genes affected
ARGLU1 (HGNC:25482): (arginine and glutamate rich 1) Enables cadherin binding activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.20619562).
BS2
High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARGLU1NM_018011.4 linkc.464G>A p.Arg155Gln missense_variant Exon 2 of 4 ENST00000400198.8 NP_060481.3 Q9NWB6-1A0A024RDW4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARGLU1ENST00000400198.8 linkc.464G>A p.Arg155Gln missense_variant Exon 2 of 4 1 NM_018011.4 ENSP00000383059.3 Q9NWB6-1
ARGLU1ENST00000360629.3 linkn.168G>A non_coding_transcript_exon_variant Exon 2 of 4 2
ARGLU1ENST00000375926.5 linkn.237G>A non_coding_transcript_exon_variant Exon 2 of 5 5
ARGLU1ENST00000472226.2 linkn.682G>A non_coding_transcript_exon_variant Exon 2 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249546
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135388
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461882
Hom.:
0
Cov.:
33
AF XY:
0.0000220
AC XY:
16
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000315
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152150
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.464G>A (p.R155Q) alteration is located in exon 2 (coding exon 2) of the ARGLU1 gene. This alteration results from a G to A substitution at nucleotide position 464, causing the arginine (R) at amino acid position 155 to be replaced by a glutamine (Q). 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
0.15
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.028
T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.15
N
REVEL
Uncertain
0.32
Sift
Benign
0.61
T
Sift4G
Benign
0.61
T
Polyphen
0.88
P
Vest4
0.47
MutPred
0.28
Loss of MoRF binding (P = 0.0328);
MVP
0.14
MPC
2.1
ClinPred
0.63
D
GERP RS
5.5
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8
Varity_R
0.21
gMVP
0.54

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.

Other links and lift over

dbSNP: rs372308355; hg19: chr13-107211889; COSMIC: COSV62271357; COSMIC: COSV62271357; API