chr15-72474873-TGGCGGCGGCGGC-T

Position:

• chr15-72474873-TGGCGGCGGCGGC-T

Variant summary

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

The NM_005744.5(ARIH1):​c.246_257delCGGCGGCGGCGG​(p.Gly83_Gly86del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000475 in 1,263,298 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: ARIH1 NM_005744.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74

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]

TMEM202-AS1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.246_257delCGGCGGCGGCGG	p.Gly83_Gly86del	disruptive_inframe_deletion	1/14	ENST00000379887.9	NP_005735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARIH1	ENST00000379887.9	c.246_257delCGGCGGCGGCGG	p.Gly83_Gly86del	disruptive_inframe_deletion	1/14	1	NM_005744.5	ENSP00000369217.4
ARIH1	ENST00000564062.1	c.240_251delCGGCGGCGGCGG	p.Gly81_Gly84del	disruptive_inframe_deletion	1/4	3		ENSP00000454774.1
TMEM202-AS1	ENST00000565181.1	n.284_295delGCCGCCGCCGCC		non_coding_transcript_exon_variant	1/1	6
ARIH1	ENST00000570085.5	n.246_257delCGGCGGCGGCGG		non_coding_transcript_exon_variant	1/5	3		ENSP00000456746.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000475 AC: 6 AN: 1263298 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 619588

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000462

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000360

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000396

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 05, 2023

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with ARIH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.246_257del, results in the deletion of 4 amino acid(s) of the ARIH1 protein (p.Gly87_Gly90del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs375614248; hg19: chr15-72767214;