Variant 6-111310079-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_001372078.1(REV3L):c.8816G>A(p.Arg2939Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000475 in 1,557,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

REV3L
NM_001372078.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69

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:

REV3L (HGNC:):

REV3L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), REV3L. . Gene score misZ 2.4677 (greater than the threshold 3.09). Trascript score misZ 3.98 (greater than threshold 3.09). GenCC has associacion of gene with Mobius syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.054683268).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REV3L	NM_001372078.1 linkuse as main transcript	c.8816G>A	p.Arg2939Gln	missense_variant	30/32	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8 linkuse as main transcript	c.8816G>A	p.Arg2939Gln	missense_variant	30/32	1	NM_001372078.1	ENSP00000357792.3		O60673-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000834

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000121

AC:

AN:

215234

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

116664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000614

Gnomad SAS exome

AF:

0.00107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000484

AC:

AN:

1405434

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

695930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.000748

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000835

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2024

The c.8816G>A (p.R2939Q) alteration is located in exon 30 (coding exon 30) of the REV3L gene. This alteration results from a G to A substitution at nucleotide position 8816, causing the arginine (R) at amino acid position 2939 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.095

T;T;.;T;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.97

.;.;D;D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.055

T;T;T;T;T

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.2

N;N;N;N;.

REVEL

Benign

0.21

Sift

Benign

0.081

T;T;T;T;.

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

1.0

D;D;.;D;.

Vest4

0.41

MutPred

0.57

Loss of phosphorylation at S2941 (P = 0.0692);Loss of phosphorylation at S2941 (P = 0.0692);.;Loss of phosphorylation at S2941 (P = 0.0692);.;

MVP

0.32

MPC

1.7

ClinPred

0.32

GERP RS

5.3

Varity_R

0.22

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over