chr15-72474873-TGGCGGCGGCGGC-T

Variant names:

• chr15-72474873-TGGCGGCGGCGGC-T
• rs375614248
• NM_005744.5:c.246_257delCGGCGGCGGCGG

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:53265): (TMEM202 antisense RNA 1)

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 rank	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.246_257delCGGCGGCGGCGG	p.Gly83_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENST00000379887.9	NP_005735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARIH1	ENST00000379887.9	c.246_257delCGGCGGCGGCGG	p.Gly83_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	1	NM_005744.5	ENSP00000369217.4

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

Apr 05, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. This variant has not been reported in the literature in individuals affected with ARIH1-related conditions. 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. -

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;