NM_005744.5:c.43G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005744.5(ARIH1):​c.43G>A​(p.Glu15Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,422,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 0.0000021 (0 hom.)
• Consequence: ARIH1 NM_005744.5 missense
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32526577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.43G>A	p.Glu15Lys	missense_variant	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>A	p.Glu15Lys	missense_variant	Exon 1 of 14	1	NM_005744.5	ENSP00000369217.4
ARIH1	ENST00000564062.1	c.37G>A	p.Glu13Lys	missense_variant	Exon 1 of 4	3		ENSP00000454774.1
TMEM202-AS1	ENST00000565181.1	n.487C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ARIH1	ENST00000570085.5	n.43G>A		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000456746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1422528 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706950

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: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.97	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.43	N
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.032	D
Polyphen		0.83	P
Vest4		0.33
MutPred		0.082		Gain of ubiquitination at E15 (P = 0.0077);
MVP		0.71
MPC		1.2
ClinPred		0.80	D
GERP RS		3.8
Varity_R		0.77
gMVP		0.19

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;