Variant 15-72474873-TGGCGGCGGCGGCGGC-TGGCGGCGGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005744.5(ARIH1):c.255_257delCGG(p.Gly86del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,406,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

ARIH1
NM_005744.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74

Variant links:

Genes affected

ARIH1 (HGNC:689): (ariadne RBR E3 ubiquitin protein ligase 1) Enables enzyme binding activity; ubiquitin-protein transferase activity; and zinc ion binding activity. Involved in protein ubiquitination. Located in Lewy body; cytoplasm; and nuclear body. Colocalizes with cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ARIH1 links:

TMEM202-AS1 (HGNC:):

TMEM202-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 868 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARIH1	NM_005744.5 linkuse as main transcript	c.255_257delCGG	p.Gly86del	disruptive_inframe_deletion	1/14	ENST00000379887.9	NP_005735.2	Q9Y4X5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARIH1	ENST00000379887.9 linkuse as main transcript	c.255_257delCGG	p.Gly86del	disruptive_inframe_deletion	1/14	1	NM_005744.5	ENSP00000369217.4	Q9Y4X5
ARIH1	ENST00000564062.1 linkuse as main transcript	c.249_251delCGG	p.Gly84del	disruptive_inframe_deletion	1/4	3		ENSP00000454774.1	H3BNB9
TMEM202-AS1	ENST00000565181.1 linkuse as main transcript	n.293_295delGCC		non_coding_transcript_exon_variant	1/1	6
ARIH1	ENST00000570085.5 linkuse as main transcript	n.255_257delCGG		non_coding_transcript_exon_variant	1/5	3		ENSP00000456746.1	H3BSK4

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00285

AC:

176

AN:

61656

Hom.:

AF XY:

0.00293

AC XY:

101

AN XY:

34494

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.00532

Gnomad ASJ exome

AF:

0.00436

Gnomad EAS exome

AF:

0.00398

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00124

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.00256

GnomAD4 exome

AF:

0.000691

AC:

868

AN:

1256872

Hom.:

AF XY:

0.000846

AC XY:

521

AN XY:

615750

show subpopulations

Gnomad4 AFR exome

AF:

0.000268

Gnomad4 AMR exome

AF:

0.00207

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.000216

Gnomad4 SAS exome

AF:

0.00440

Gnomad4 FIN exome

AF:

0.00149

Gnomad4 NFE exome

AF:

0.000428

Gnomad4 OTH exome

AF:

0.000683

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73142

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000149

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 24, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with ARIH1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.255_257del, results in the deletion of 1 amino acid(s) of the ARIH1 protein (p.Gly90del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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