chr15-72474682-G-T

Variant names:

• chr15-72474682-G-T
• NM_005744.5:c.43G>T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_005744.5(ARIH1):​c.43G>T​(p.Glu15*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000703 in 1,422,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ARIH1 NM_005744.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.87

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_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.974 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.43G>T	p.Glu15*	stop_gained	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.43G>T	p.Glu15*	stop_gained	Exon 1 of 14	1	NM_005744.5	ENSP00000369217.4
ARIH1	ENST00000564062.1	c.37G>T	p.Glu13*	stop_gained	Exon 1 of 4	3		ENSP00000454774.1
TMEM202-AS1	ENST00000565181.1	n.487C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ARIH1	ENST00000570085.5	n.43G>T		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000456746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422524 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 706948

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.59
CADD	Pathogenic	38
DANN	Uncertain	1.0
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Benign	0.74	D
Vest4		0.33
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-72767023;