15-72474755-C-G

Variant names:

• chr15-72474755-C-G
• rs751293008
• NM_005744.5:c.116C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005744.5(ARIH1):​c.116C>G​(p.Thr39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,401,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T39I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ARIH1 NM_005744.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046472073).

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.116C>G	p.Thr39Ser	missense	Exon 1 of 14	NP_005735.2	Q9Y4X5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARIH1	ENST00000379887.9	TSL:1 MANE Select	c.116C>G	p.Thr39Ser	missense	Exon 1 of 14	ENSP00000369217.4	Q9Y4X5
	ARIH1	ENST00000915026.1		c.116C>G	p.Thr39Ser	missense	Exon 1 of 14	ENSP00000585085.1
	ARIH1	ENST00000915024.1		c.116C>G	p.Thr39Ser	missense	Exon 1 of 14	ENSP00000585083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1401266 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 697356

African (AFR) AF: 0.00 AC: 0 AN: 29030

American (AMR) AF: 0.00 AC: 0 AN: 37530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24196

East Asian (EAS) AF: 0.00 AC: 0 AN: 32850

South Asian (SAS) AF: 0.00 AC: 0 AN: 79686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5570

European-Non Finnish (NFE) AF: 9.24e-7 AC: 1 AN: 1082602

Other (OTH) AF: 0.00 AC: 0 AN: 57458

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.070	N
REVEL	Benign	0.17
Sift	Benign	0.30	T
Sift4G	Benign	0.42	T
Polyphen		0.0010	B
Vest4		0.087
MutPred		0.21		Loss of glycosylation at T39 (P = 0.1631)
MVP		0.32
MPC		0.96
ClinPred		0.13	T
GERP RS		2.7
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.055
gMVP		0.035
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs751293008; hg19: chr15-72767096;