Variant 9-137605832-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152285.4(ARRDC1):c.115C>G(p.Arg39Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000907 in 1,102,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

ARRDC1
NM_152285.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.571

Variant links:

Genes affected

ARRDC1 (HGNC:28633): (arrestin domain containing 1) Enables several functions, including arrestin family protein binding activity; ubiquitin ligase-substrate adaptor activity; and ubiquitin protein ligase binding activity. Involved in several processes, including cellular protein metabolic process; extracellular vesicle biogenesis; and negative regulation of Notch signaling pathway. Located in cytoplasmic vesicle; extracellular vesicle; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARRDC1 links:

ARRDC1 (HGNC:):

ARRDC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRDC1	NM_152285.4 linkuse as main transcript	c.115C>G	p.Arg39Gly	missense_variant	1/8	ENST00000371421.9	NP_689498.1	Q8N5I2
ARRDC1	NM_001317968.2 linkuse as main transcript	c.115C>G	p.Arg39Gly	missense_variant	1/7		NP_001304897.1
ARRDC1	XM_005266119.2 linkuse as main transcript	c.115C>G	p.Arg39Gly	missense_variant	1/7		XP_005266176.1
ARRDC1	XM_047424069.1 linkuse as main transcript	c.115C>G	p.Arg39Gly	missense_variant	1/8		XP_047280025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRDC1	ENST00000371421.9 linkuse as main transcript	c.115C>G	p.Arg39Gly	missense_variant	1/8	1	NM_152285.4	ENSP00000360475.4		Q8N5I2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.07e-7

AC:

AN:

1102080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

527640

show subpopulations

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:

0.0000315

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.115C>G (p.R39G) alteration is located in exon 1 (coding exon 1) of the ARRDC1 gene. This alteration results from a C to G substitution at nucleotide position 115, causing the arginine (R) at amino acid position 39 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

T;.;.

Eigen

Benign

0.071

Eigen_PC

Benign

0.092

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.51

T;T;T

M_CAP

Pathogenic

0.73

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

0.39

B;P;P

Vest4

0.21

MutPred

0.83

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.29

MPC

0.26

ClinPred

0.77

GERP RS

4.2

Varity_R

0.39

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over