6-111372921-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001372078.1(REV3L):c.5434G>C(p.Asp1812His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,614,002 control chromosomes in the GnomAD database, including 342 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 0.014 ( 22 hom., cov: 32)

Exomes 𝑓: 0.019 ( 320 hom. )

Consequence

REV3L
NM_001372078.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.43

Publications

16 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=0.007606685).

BP6

Variant 6-111372921-C-G is Benign according to our data. Variant chr6-111372921-C-G is described in ClinVar as Benign. ClinVar VariationId is 3041876.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0139 (2111/152246) while in subpopulation NFE AF = 0.02 (1359/68012). AF 95% confidence interval is 0.0191. There are 22 homozygotes in GnomAd4. There are 1036 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2111 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1 link	c.5434G>C	p.Asp1812His	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.5434G>C	p.Asp1812His	missense_variant	Exon 13 of 32	1	NM_001372078.1	ENSP00000357792.3		O60673-1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2111

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0220

GnomAD2 exomes

AF:

0.0142

AC:

3561

AN:

251326

AF XY:

0.0140

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0213

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.0190

AC:

27809

AN:

1461756

Hom.:

320

Cov.:

AF XY:

0.0186

AC XY:

13497

AN XY:

727178

show subpopulations

African (AFR)

AF:

0.00338

AC:

113

AN:

33478

American (AMR)

AF:

0.0157

AC:

703

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

400

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000742

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.0154

AC:

824

AN:

53360

Middle Eastern (MID)

AF:

0.00936

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0221

AC:

24583

AN:

1111962

Other (OTH)

AF:

0.0177

AC:

1068

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

1553

3107

4660

6214

7767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.0139

AC:

2111

AN:

152246

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

1036

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00419

AC:

174

AN:

41560

American (AMR)

AF:

0.0184

AC:

281

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.000624

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0165

AC:

175

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0200

AC:

1359

AN:

68012

Other (OTH)

AF:

0.0218

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

106

213

319

426

532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0176

Hom.:

Bravo

AF:

0.0147

TwinsUK

AF:

0.0186

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.0217

AC:

187

ExAC

AF:

0.0135

AC:

1635

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0213

EpiControl

AF:

0.0214

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

REV3L-related disorder

Benign:1

Mar 14, 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

0.17

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;T;.;T

Eigen

Benign

-0.077

Eigen_PC

Benign

0.071

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.77

.;.;T;T

MetaRNN

Benign

0.0076

T;T;T;T

MetaSVM

Benign

-0.89

PhyloP100

3.4

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.090

B;B;.;B

Vest4

0.16

MPC

0.076

ClinPred

0.0075

GERP RS

5.1

Varity_R

0.042

gMVP

0.32

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over