15-72474682-G-C

Variant names:

• chr15-72474682-G-C
• rs1052050835
• NM_005744.5:c.43G>C

Variant summary

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

The NM_005744.5(ARIH1):​c.43G>C​(p.Glu15Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARIH1 NM_005744.5 missense
• Clinical Significance: association no assertion criteria provided O:1
• 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=0.32282934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARIH1	NM_005744.5	c.43G>C	p.Glu15Gln	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>C	p.Glu15Gln	missense_variant	Exon 1 of 14	1	NM_005744.5	ENSP00000369217.4
ARIH1	ENST00000564062.1	c.37G>C	p.Glu13Gln	missense_variant	Exon 1 of 4	3		ENSP00000454774.1
TMEM202-AS1	ENST00000565181.1	n.487C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ARIH1	ENST00000570085.5	n.43G>C		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000456746.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Aortic aneurysm Other:1

-

University of Washington Center for Mendelian Genomics, University of Washington

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.22	N
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.039	D
Polyphen		0.83	P
Vest4		0.27
MVP		0.69
MPC		1.1
ClinPred		0.84	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.64
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs1052050835; hg19: chr15-72767023;