Genetic Variant UVRAG:p.Ser2Arg (chr11-75815413-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003369.4(UVRAG):c.6C>A(p.Ser2Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000321 in 1,246,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

UVRAG
NM_003369.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.973

Publications

0 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:

UVRAG-DT (HGNC:):

UVRAG-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18171048).

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.6C>A	p.Ser2Arg	missense	Exon 1 of 15	NP_003360.2
UVRAG	NM_001386671.1		c.6C>A	p.Ser2Arg	missense	Exon 1 of 16	NP_001373600.1
UVRAG	NM_001386672.1		c.6C>A	p.Ser2Arg	missense	Exon 1 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.6C>A	p.Ser2Arg	missense	Exon 1 of 15	ENSP00000348455.3	Q9P2Y5-1
UVRAG	ENST00000876952.1		c.6C>A	p.Ser2Arg	missense	Exon 1 of 16	ENSP00000547011.1
UVRAG	ENST00000969466.1		c.6C>A	p.Ser2Arg	missense	Exon 1 of 15	ENSP00000639525.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.14e-7

AC:

AN:

1094394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

520650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22954

American (AMR)

AF:

0.00

AC:

AN:

8474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14568

East Asian (EAS)

AF:

0.00

AC:

AN:

26630

South Asian (SAS)

AF:

0.00

AC:

AN:

26704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3230

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

925624

Other (OTH)

AF:

0.00

AC:

AN:

44134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000197

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.00

Hom.:

Bravo

AF:

0.0000227

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

0.54

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.072

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.52

M_CAP

Benign

0.019

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.97

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.31

REVEL

Benign

0.15

Sift

Uncertain

0.011

Sift4G

Pathogenic

0.0

Polyphen

0.31

Vest4

0.23

MutPred

0.25

Gain of MoRF binding (P = 0.0015)

MVP

0.13

MPC

0.32

ClinPred

0.91

GERP RS

4.2

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.20

gMVP

0.57

Mutation Taster

=98/2

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