chr6-111322635-C-T

Variant names:

• chr6-111322635-C-T
• rs3218592
• NM_001372078.1:c.8285G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001372078.1(REV3L):​c.8285G>A​(p.Arg2762Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000341 in 1,614,080 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (5 hom.)
• Consequence: REV3L NM_001372078.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 3.93
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009132206).
• BP6: Variant 6-111322635-C-T is Benign according to our data. Variant chr6-111322635-C-T is described in ClinVar as Benign. ClinVar VariationId is 715342.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 96 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372078.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	NM_001372078.1	MANE Select	c.8285G>A	p.Arg2762Gln	missense	Exon 26 of 32	NP_001359007.1	O60673-1
	REV3L	NM_002912.5		c.8285G>A	p.Arg2762Gln	missense	Exon 27 of 33	NP_002903.3	O60673-1
	REV3L	NM_001286431.2		c.8051G>A	p.Arg2684Gln	missense	Exon 29 of 35	NP_001273360.1	O60673-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	ENST00000368802.8	TSL:1 MANE Select	c.8285G>A	p.Arg2762Gln	missense	Exon 26 of 32	ENSP00000357792.3	O60673-1
	REV3L	ENST00000358835.7	TSL:5	c.8285G>A	p.Arg2762Gln	missense	Exon 27 of 33	ENSP00000351697.3	O60673-1
	REV3L	ENST00000435970.5	TSL:2	c.8051G>A	p.Arg2684Gln	missense	Exon 28 of 34	ENSP00000402003.1	O60673-2

Frequencies

GnomAD3 genomes AF: 0.000624 AC: 95 AN: 152176 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00105 AC: 265 AN: 251438 AF XY: 0.000957

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0137

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000311 AC: 454 AN: 1461786 Hom.: 5 Cov.: 30 AF XY: 0.000301 AC XY: 219 AN XY: 727196

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00958 AC: 380 AN: 39676

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111950

Other (OTH) AF: 0.000911 AC: 55 AN: 60388

GnomAD4 genome AF: 0.000630 AC: 96 AN: 152294 Hom.: 1 Cov.: 32 AF XY: 0.000712 AC XY: 53 AN XY: 74482

African (AFR) AF: 0.000529 AC: 22 AN: 41552

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000309 Hom.: 0

Bravo AF: 0.000740

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000807 AC: 98

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	REV3L-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.085
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.039
Sift	Benign	0.063	T
Sift4G	Uncertain	0.015	D
Polyphen		0.10	B
Vest4		0.25
MVP		0.14
MPC		0.76
ClinPred		0.063	T
GERP RS		3.8
Varity_R		0.26
gMVP		0.86
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3218592; hg19: chr6-111643838; COSMIC: COSV107443437;