Variant 6-111307394-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001372078.1(REV3L):c.9219G>C(p.Arg3073=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 1,613,480 control chromosomes in the GnomAD database, including 14,809 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1020 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13789 hom. )

Consequence

REV3L
NM_001372078.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0860

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 6-111307394-C-G is Benign according to our data. Variant chr6-111307394-C-G is described in ClinVar as [Benign]. Clinvar id is 1243274.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.086 with no splicing effect.

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/exons	MANE	Protein	UniProt
REV3L	NM_001372078.1 linkuse as main transcript	c.9219G>C	p.Arg3073=	synonymous_variant	31/32	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.9219G>C	p.Arg3073=	synonymous_variant	31/32	1	NM_001372078.1	ENSP00000357792	P4	O60673-1

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15323

AN:

152050

Hom.:

1022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0553

Gnomad FIN

AF:

0.0996

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.129

GnomAD3 exomes

AF:

0.104

AC:

26082

AN:

251442

Hom.:

1753

AF XY:

0.107

AC XY:

14522

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.0841

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0536

Gnomad FIN exome

AF:

0.0977

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.130

AC:

190118

AN:

1461312

Hom.:

13789

Cov.:

AF XY:

0.129

AC XY:

93710

AN XY:

726964

show subpopulations

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.0867

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0547

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.101

AC:

15308

AN:

152168

Hom.:

1020

Cov.:

AF XY:

0.0989

AC XY:

7357

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0254

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0550

Gnomad4 FIN

AF:

0.0996

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.127

Alfa

AF:

0.118

Hom.:

395

Bravo

AF:

0.100

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

REV3L-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 2019

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

3.4

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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