Variant chr9-137605818-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000371421.9(ARRDC1):c.101C>T(p.Ala34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000892 in 1,121,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

ARRDC1
ENST00000371421.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.327

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.101C>T	p.Ala34Val	missense_variant	1/8	ENST00000371421.9	NP_689498.1	Q8N5I2
ARRDC1	NM_001317968.2 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	1/7		NP_001304897.1
ARRDC1	XM_005266119.2 linkuse as main transcript	c.101C>T	p.Ala34Val	missense_variant	1/7		XP_005266176.1
ARRDC1	XM_047424069.1 linkuse as main transcript	c.101C>T	p.Ala34Val	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.101C>T	p.Ala34Val	missense_variant	1/8	1	NM_152285.4	ENSP00000360475.4		Q8N5I2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.92e-7

AC:

AN:

1121394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

540182

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000106

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

Jul 12, 2022

The c.101C>T (p.A34V) alteration is located in exon 1 (coding exon 1) of the ARRDC1 gene. This alteration results from a C to T substitution at nucleotide position 101, causing the alanine (A) at amino acid position 34 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.75

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.039

D;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.17

B;P;B

Vest4

0.21

MutPred

0.39

Loss of methylation at R29 (P = 0.1089);Loss of methylation at R29 (P = 0.1089);Loss of methylation at R29 (P = 0.1089);

MVP

0.29

MPC

0.19

ClinPred

0.70

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.072

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: -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