rs458017

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001372078.1(REV3L):c.3467A>G(p.Tyr1156Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 1,613,740 control chromosomes in the GnomAD database, including 3,293 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.056 ( 271 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3022 hom. )

Consequence

REV3L
NM_001372078.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.168

Publications

47 publications found

Variant links:

Genes affected

REV3L (HGNC:9968): (REV3 like, DNA directed polymerase zeta catalytic subunit) The protein encoded by this gene represents the catalytic subunit of DNA polymerase zeta, which functions in translesion DNA synthesis. The encoded protein can be found in mitochondria, where it protects DNA from damage. Defects in this gene are a cause of Mobius syndrome. [provided by RefSeq, Jan 2017]

REV3L links:

MFSD4B (HGNC:21053): (major facilitator superfamily domain containing 4B) Predicted to enable glucose transmembrane transporter activity. Predicted to be involved in glucose transmembrane transport and sodium ion transport. Predicted to be located in apical plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFSD4B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019741356).

BP6

Variant 6-111374888-T-C is Benign according to our data. Variant chr6-111374888-T-C is described in ClinVar as Benign. ClinVar VariationId is 3037951.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1 link	c.3467A>G	p.Tyr1156Cys	missense_variant	Exon 13 of 32	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8 link	c.3467A>G	p.Tyr1156Cys	missense_variant	Exon 13 of 32	1	NM_001372078.1	ENSP00000357792.3		O60673-1

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8537

AN:

152140

Hom.:

272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0443

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.0476

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0445

Gnomad FIN

AF:

0.0619

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0633

Gnomad OTH

AF:

0.0726

GnomAD2 exomes

AF:

0.0593

AC:

14855

AN:

250414

AF XY:

0.0598

show subpopulations

Gnomad AFR exome

AF:

0.0452

Gnomad AMR exome

AF:

0.0613

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.0671

Gnomad NFE exome

AF:

0.0631

Gnomad OTH exome

AF:

0.0666

GnomAD4 exome

AF:

0.0618

AC:

90370

AN:

1461482

Hom.:

3022

Cov.:

AF XY:

0.0619

AC XY:

44974

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.0437

AC:

1462

AN:

33462

American (AMR)

AF:

0.0612

AC:

2732

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3847

AN:

26114

East Asian (EAS)

AF:

0.000176

AC:

AN:

39696

South Asian (SAS)

AF:

0.0530

AC:

4566

AN:

86156

European-Finnish (FIN)

AF:

0.0667

AC:

3561

AN:

53402

Middle Eastern (MID)

AF:

0.0799

AC:

461

AN:

5768

European-Non Finnish (NFE)

AF:

0.0628

AC:

69807

AN:

1111852

Other (OTH)

AF:

0.0651

AC:

3927

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

5068

10137

15205

20274

25342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2594

5188

7782

10376

12970

<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:

0.0561

AC:

8539

AN:

152258

Hom.:

271

Cov.:

AF XY:

0.0542

AC XY:

4038

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0442

AC:

1837

AN:

41552

American (AMR)

AF:

0.0476

AC:

728

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

480

AN:

3468

East Asian (EAS)

AF:

0.00193

AC:

AN:

5190

South Asian (SAS)

AF:

0.0446

AC:

215

AN:

4824

European-Finnish (FIN)

AF:

0.0619

AC:

656

AN:

10600

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0634

AC:

4309

AN:

68014

Other (OTH)

AF:

0.0718

AC:

152

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

419

838

1257

1676

2095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0628

Hom.:

1583

Bravo

AF:

0.0562

TwinsUK

AF:

0.0653

AC:

242

ALSPAC

AF:

0.0615

AC:

237

ESP6500AA

AF:

0.0477

AC:

210

ESP6500EA

AF:

0.0673

AC:

579

ExAC

AF:

0.0570

AC:

6924

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0674

EpiControl

AF:

0.0640

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

REV3L-related disorder

Benign:1

Mar 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.12

T;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.41

.;.;T;T

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-0.94

PhyloP100

0.17

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.82

N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.26

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.0020

B;B;.;B

Vest4

0.092

MPC

0.077

ClinPred

0.00060

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.049

gMVP

0.30

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over