chr15-72474873-TGGCGGCGGCGGCGGCGGC-T

Variant names:

• chr15-72474873-TGGCGGCGGCGGCGGCGGC-T
• rs375614248
• NM_005744.5:c.240_257delCGGCGGCGGCGGCGGCGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005744.5(ARIH1):​c.240_257delCGGCGGCGGCGGCGGCGG​(p.Gly81_Gly86del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000158 in 1,263,316 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: ARIH1 NM_005744.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.74
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005744.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	NM_005744.5	MANE Select	c.240_257delCGGCGGCGGCGGCGGCGG	p.Gly81_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	NP_005735.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.240_257delCGGCGGCGGCGGCGGCGG	p.Gly81_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000369217.4
	ARIH1	ENST00000915026.1		c.240_257delCGGCGGCGGCGGCGGCGG	p.Gly81_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.240_257delCGGCGGCGGCGGCGGCGG	p.Gly81_Gly86del	disruptive_inframe_deletion	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1263316 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 619602

African (AFR) AF: 0.00 AC: 0 AN: 26224

American (AMR) AF: 0.00 AC: 0 AN: 21626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20236

East Asian (EAS) AF: 0.00 AC: 0 AN: 27798

South Asian (SAS) AF: 0.00 AC: 0 AN: 58510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4986

European-Non Finnish (NFE) AF: 0.00000198 AC: 2 AN: 1009638

Other (OTH) AF: 0.00 AC: 0 AN: 51510

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.7

Splicing

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

Other links and lift over

dbSNP: rs375614248; hg19: chr15-72767214;