chr15-72474873-T-TGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr15-72474873-T-TGGCGGCGGCGGCGGCGGCGGC
• rs375614248
• NM_005744.5:c.237_257dupCGGCGGCGGCGGCGGCGGCGG

Variant summary

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

The NM_005744.5(ARIH1):​c.237_257dupCGGCGGCGGCGGCGGCGGCGG​(p.Gly80_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 0.00000668 in 149,696 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 INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G86G) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000067 (0 hom., cov: 32)
• Consequence: ARIH1 NM_005744.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 1 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.237_257dupCGGCGGCGGCGGCGGCGGCGG	p.Gly80_Gly86dup	disruptive_inframe_insertion	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.237_257dupCGGCGGCGGCGGCGGCGGCGG	p.Gly80_Gly86dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000369217.4
	ARIH1	ENST00000915026.1		c.237_257dupCGGCGGCGGCGGCGGCGGCGG	p.Gly80_Gly86dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.237_257dupCGGCGGCGGCGGCGGCGGCGG	p.Gly80_Gly86dup	disruptive_inframe_insertion	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149696 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149696 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73034

African (AFR) AF: 0.00 AC: 0 AN: 40650

American (AMR) AF: 0.0000663 AC: 1 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67346

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=82/18	polymorphism

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;