Genetic Variant ARGLU1:p.Ter274Ter (chr13-106543996-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_018011.4(ARGLU1):c.822A>G(p.Ter274Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000922 in 1,582,790 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 1 hom. )

Consequence

ARGLU1
NM_018011.4 stop_retained

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.25

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]

ARGLU1 links:

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 (BayesDel_noAF=-0.46).

BP6

Variant 13-106543996-T-C is Benign according to our data. Variant chr13-106543996-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034677.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.25 with no splicing effect.

BS2

High AC in GnomAd4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARGLU1	NM_018011.4 link	c.822A>G	p.Ter274Ter	stop_retained_variant	Exon 4 of 4	ENST00000400198.8	NP_060481.3	Q9NWB6-1A0A024RDW4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARGLU1	ENST00000400198.8 link	c.822A>G	p.Ter274Ter	stop_retained_variant	Exon 4 of 4	1	NM_018011.4	ENSP00000383059.3	Q9NWB6-1
ARGLU1	ENST00000375926.5 link	n.653A>G		non_coding_transcript_exon_variant	Exon 5 of 5	5
ARGLU1	ENST00000472226.2 link	n.3340A>G		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

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:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000879

AC:

AN:

216204

Hom.:

AF XY:

0.0000679

AC XY:

AN XY:

117892

show subpopulations

Gnomad AFR exome

AF:

0.000730

Gnomad AMR exome

AF:

0.0000751

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:

0.0000594

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1430570

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

710496

show subpopulations

Gnomad4 AFR exome

AF:

0.000679

Gnomad4 AMR exome

AF:

0.0000540

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000517

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000361

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.000355

Asia WGS

AF:

0.000578

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ARGLU1-related disorder

Benign:1

Aug 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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