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GeneBe

6-111307394-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts 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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.086 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
REV3LNM_001372078.1 linkuse as main transcriptc.9219G>C p.Arg3073= synonymous_variant 31/32 ENST00000368802.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
REV3LENST00000368802.8 linkuse as main transcriptc.9219G>C p.Arg3073= synonymous_variant 31/321 NM_001372078.1 P4O60673-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.101
AC:
15323
AN:
152050
Hom.:
1022
Cov.:
32
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.:
32
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.101
AC:
15308
AN:
152168
Hom.:
1020
Cov.:
32
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, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

REV3L-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJun 07, 2019This 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 submitterclinical testingGeneDxMay 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.

Other links and lift over

dbSNP: rs3204954; hg19: chr6-111628597; API