6-111473206-T-G

Variant names:

• chr6-111473206-T-G
• rs6900341
• NM_001372078.1:c.139+9544A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001372078.1(REV3L):​c.139+9544A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 148,784 control chromosomes in the GnomAD database, including 8,435 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8435 hom., cov: 31)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 19 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]

REV3L Gene-Disease associations (from GenCC):

• Mobius syndrome

  Inheritance: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Laboratory for Molecular Medicine, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REV3L	NM_001372078.1	c.139+9544A>C		intron_variant	Intron 1 of 31	ENST00000368802.8	NP_001359007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REV3L	ENST00000368802.8	c.139+9544A>C		intron_variant	Intron 1 of 31	1	NM_001372078.1	ENSP00000357792.3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 45981 AN: 148662 Hom.: 8428 Cov.: 31

Gnomad AFR AF: 0.0859

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.340

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46003 AN: 148784 Hom.: 8435 Cov.: 31 AF XY: 0.312 AC XY: 22629 AN XY: 72576

African (AFR) AF: 0.0857 AC: 3385 AN: 39496

American (AMR) AF: 0.381 AC: 5659 AN: 14872

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3466

East Asian (EAS) AF: 0.403 AC: 2039 AN: 5056

South Asian (SAS) AF: 0.432 AC: 2036 AN: 4714

European-Finnish (FIN) AF: 0.376 AC: 3834 AN: 10186

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26589 AN: 67724

Other (OTH) AF: 0.337 AC: 698 AN: 2072

Alfa AF: 0.363 Hom.: 34657

Bravo AF: 0.295

Asia WGS AF: 0.372 AC: 1294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.70
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs6900341; hg19: chr6-111794409; COSMIC: COSV62622861;