Genetic Variant NM_003369.4:c.211T>C (chr11-75851976-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003369.4(UVRAG):c.211T>C(p.Cys71Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000139 in 1,611,746 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

UVRAG
NM_003369.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.37

Publications

3 publications found

Variant links:

Genes affected

UVRAG (HGNC:12640): (UV radiation resistance associated) This gene complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells and encodes a protein with a C2 domain. The protein activates the Beclin1-PI(3)KC3 complex, promoting autophagy and suppressing the proliferation and tumorigenicity of human colon cancer cells. Chromosomal aberrations involving this gene are associated with left-right axis malformation and mutations in this gene have been associated with colon cancer. [provided by RefSeq, Jul 2008]

UVRAG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22265464).

BS2

High AC in GnomAd4 at 74 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003369.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UVRAG	NM_003369.4	MANE Select	c.211T>C	p.Cys71Arg	missense	Exon 2 of 15	NP_003360.2
UVRAG	NM_001386671.1		c.211T>C	p.Cys71Arg	missense	Exon 2 of 16	NP_001373600.1
UVRAG	NM_001386672.1		c.211T>C	p.Cys71Arg	missense	Exon 2 of 14	NP_001373601.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UVRAG	ENST00000356136.8	TSL:1 MANE Select	c.211T>C	p.Cys71Arg	missense	Exon 2 of 15	ENSP00000348455.3	Q9P2Y5-1
UVRAG	ENST00000876952.1		c.211T>C	p.Cys71Arg	missense	Exon 2 of 16	ENSP00000547011.1
UVRAG	ENST00000969466.1		c.211T>C	p.Cys71Arg	missense	Exon 2 of 15	ENSP00000639525.1

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000204

AC:

AN:

250208

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.000525

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000794

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000103

AC:

150

AN:

1459392

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

726088

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

33386

American (AMR)

AF:

0.000494

AC:

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000558

AC:

AN:

1110392

Other (OTH)

AF:

0.000249

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000486

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41576

American (AMR)

AF:

0.000392

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.000285

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

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

Uncertain

0.55

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

M_CAP

Benign

0.025

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.1

PhyloP100

6.4

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.27

Sift

Uncertain

0.021

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.93

MVP

0.13

MPC

1.1

ClinPred

0.030

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.87

Mutation Taster

=74/26

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