NM_001372078.1:c.9190G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001372078.1(REV3L):c.9190G>A(p.Val3064Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,776 control chromosomes in the GnomAD database, including 14,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1017 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13793 hom. )

Consequence

REV3L
NM_001372078.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.69

Publications

32 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016376078).

BP6

Variant 6-111307423-C-T is Benign according to our data. Variant chr6-111307423-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267973.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1 link	c.9190G>A	p.Val3064Ile	missense_variant	Exon 31 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.9190G>A	p.Val3064Ile	missense_variant	Exon 31 of 32	1	NM_001372078.1	ENSP00000357792.3		O60673-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15317

AN:

152110

Hom.:

1019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.0791

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0552

Gnomad FIN

AF:

0.0993

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.104

AC:

26096

AN:

251464

AF XY:

0.107

show subpopulations

Gnomad AFR exome

AF:

0.0216

Gnomad AMR exome

AF:

0.0842

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0977

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.130

AC:

190234

AN:

1461548

Hom.:

13793

Cov.:

AF XY:

0.129

AC XY:

93774

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.0220

AC:

735

AN:

33474

American (AMR)

AF:

0.0867

AC:

3879

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

4379

AN:

26130

East Asian (EAS)

AF:

0.000176

AC:

AN:

39700

South Asian (SAS)

AF:

0.0547

AC:

4720

AN:

86252

European-Finnish (FIN)

AF:

0.101

AC:

5370

AN:

53420

Middle Eastern (MID)

AF:

0.167

AC:

964

AN:

5766

European-Non Finnish (NFE)

AF:

0.146

AC:

162249

AN:

1111692

Other (OTH)

AF:

0.131

AC:

7931

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

9367

18733

28100

37466

46833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5560

11120

16680

22240

27800

<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:

0.101

AC:

15302

AN:

152228

Hom.:

1017

Cov.:

AF XY:

0.0988

AC XY:

7354

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0253

AC:

1052

AN:

41552

American (AMR)

AF:

0.123

AC:

1876

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

581

AN:

3468

East Asian (EAS)

AF:

0.000966

AC:

AN:

5178

South Asian (SAS)

AF:

0.0549

AC:

265

AN:

4830

European-Finnish (FIN)

AF:

0.0993

AC:

1051

AN:

10588

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.148

AC:

10076

AN:

68008

Other (OTH)

AF:

0.127

AC:

267

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

702

1404

2107

2809

3511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<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:

0.133

Hom.:

4955

Bravo

AF:

0.100

TwinsUK

AF:

0.145

AC:

538

ALSPAC

AF:

0.146

AC:

564

ESP6500AA

AF:

0.0259

AC:

114

ESP6500EA

AF:

0.151

AC:

1296

ExAC

AF:

0.102

AC:

12398

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.159

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

REV3L-related disorder

Benign:1

Jun 07, 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). -

not provided

Benign:1

May 17, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.094

T;T;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

.;.;D;D

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

7.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.73

N;N;N;N

REVEL

Benign

0.079

Sift

Benign

0.038

D;D;D;D

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.39

B;B;.;B

Vest4

0.11

MPC

1.3

ClinPred

0.026

GERP RS

5.7

Varity_R

0.32

gMVP

0.58

Mutation Taster

=99/1

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

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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