Variant 15-72474873-TGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGC 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.249_257dupCGGCGGCGG(p.Gly84_Gly86dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 1,412,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ARIH1
NM_005744.5 disruptive_inframe_insertion

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 GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARIH1	NM_005744.5 linkuse as main transcript	c.249_257dupCGGCGGCGG	p.Gly84_Gly86dup	disruptive_inframe_insertion	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.249_257dupCGGCGGCGG	p.Gly84_Gly86dup	disruptive_inframe_insertion	1/14	1	NM_005744.5	ENSP00000369217.4	Q9Y4X5
ARIH1	ENST00000564062.1 linkuse as main transcript	c.243_251dupCGGCGGCGG	p.Gly82_Gly84dup	disruptive_inframe_insertion	1/4	3		ENSP00000454774.1	H3BNB9
TMEM202-AS1	ENST00000565181.1 linkuse as main transcript	n.287_295dupGCCGCCGCC		non_coding_transcript_exon_variant	1/1	6
ARIH1	ENST00000570085.5 linkuse as main transcript	n.249_257dupCGGCGGCGG		non_coding_transcript_exon_variant	1/5	3		ENSP00000456746.1	H3BSK4

Frequencies

GnomAD3 genomes

AF:

0.0000468

AC:

AN:

149696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000428

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000594

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

61656

Hom.:

AF XY:

0.0000290

AC XY:

AN XY:

34494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000188

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000245

AC:

AN:

1263298

Hom.:

Cov.:

AF XY:

0.0000339

AC XY:

AN XY:

619588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000462

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000205

Gnomad4 FIN exome

AF:

0.0000234

Gnomad4 NFE exome

AF:

0.0000158

Gnomad4 OTH exome

AF:

0.0000194

GnomAD4 genome

AF:

0.0000468

AC:

AN:

149696

Hom.:

Cov.:

AF XY:

0.0000548

AC XY:

AN XY:

73034

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000428

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000594

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

Dec 09, 2023

This variant, c.249_257dup, results in the insertion of 3 amino acid(s) of the ARIH1 protein (p.Gly88_Gly90dup), but otherwise preserves the integrity of the reading frame. 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 has not been reported in the literature in individuals affected with ARIH1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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