15-72474786-G-T

Position:

• chr15-72474786-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005744.5(ARIH1):​c.147G>T​(p.Glu49Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000587 in 1,362,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: ARIH1 NM_005744.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12861073).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.147G>T	p.Glu49Asp	missense_variant	1/14	ENST00000379887.9	NP_005735.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARIH1	ENST00000379887.9	c.147G>T	p.Glu49Asp	missense_variant	1/14	1	NM_005744.5	ENSP00000369217.4
ARIH1	ENST00000564062.1	c.141G>T	p.Glu47Asp	missense_variant	1/4	3		ENSP00000454774.1
TMEM202-AS1	ENST00000565181.1	n.383C>A		non_coding_transcript_exon_variant	1/1	6
ARIH1	ENST00000570085.5	n.147G>T		non_coding_transcript_exon_variant	1/5	3		ENSP00000456746.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000526 AC: 1 AN: 189988 Hom.: 0 AF XY: 0.00000949 AC XY: 1 AN XY: 105422

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000587 AC: 8 AN: 1362320 Hom.: 0 Cov.: 31 AF XY: 0.00000591 AC XY: 4 AN XY: 676286

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000315

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000660

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000378 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.77	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.55	N
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	0.21	N
REVEL	Benign	0.21
Sift	Benign	0.44	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.086
MutPred		0.31		Loss of sheet (P = 0.1158);
MVP		0.31
MPC		0.97
ClinPred		0.28	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.059

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs749268378; hg19: chr15-72767127;