Genetic Variant NM_001080523.3:c.403A>G (chr19-4896727-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001080523.3(ARRDC5):c.403A>G(p.Arg135Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000327 in 1,613,608 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

ARRDC5
NM_001080523.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.272

Publications

0 publications found

Variant links:

Genes affected

ARRDC5 (HGNC:31407): (arrestin domain containing 5) Predicted to enable ubiquitin ligase-substrate adaptor activity and ubiquitin protein ligase binding activity. Predicted to be involved in protein transport. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ARRDC5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.096116155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080523.3. 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
	ARRDC5	NM_001080523.3	MANE Select	c.403A>G	p.Arg135Gly	missense	Exon 2 of 3	NP_001073992.2	A0A494BZV3
	ARRDC5	NM_001367189.2		c.469A>G	p.Arg157Gly	missense	Exon 3 of 4	NP_001354118.1	A0ABB0MV98

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARRDC5	ENST00000650722.2	MANE Select	c.403A>G	p.Arg135Gly	missense	Exon 2 of 3	ENSP00000498235.1	A0A494BZV3
ARRDC5	ENST00000718248.1		c.469A>G	p.Arg157Gly	missense	Exon 3 of 4	ENSP00000520693.1	A0ABB0MV98
ARRDC5	ENST00000718249.1		n.*9A>G		non_coding_transcript_exon	Exon 2 of 3	ENSP00000520694.1	A0ABB0MV92

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000164

AC:

AN:

249268

AF XY:

0.000141

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000340

AC:

497

AN:

1461542

Hom.:

Cov.:

AF XY:

0.000276

AC XY:

201

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000433

AC:

481

AN:

1111730

Other (OTH)

AF:

0.000149

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000197

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000247

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000726

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.14

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.57

M_CAP

Benign

0.0089

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

0.27

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.081

Sift

Benign

0.10

Sift4G

Uncertain

0.047

Polyphen

0.50

Vest4

0.41

MVP

0.15

MPC

0.24

ClinPred

0.13

GERP RS

3.8

Varity_R

0.19

gMVP

0.65

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over