rs465646

Positions:

• chr6-111299555-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001372078.1(REV3L):​c.*461C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.806 in 152,736 control chromosomes in the GnomAD database, including 49,778 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 0.81 (49604 hom., cov: 34)
  • Exomes 𝑓: 0.81 (174 hom.)
• Consequence: REV3L NM_001372078.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REV3L	NM_001372078.1	c.*461C>T		3_prime_UTR_variant	32/32	ENST00000368802.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REV3L	ENST00000368802.8	c.*461C>T		3_prime_UTR_variant	32/32	1	NM_001372078.1	P4

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122554 AN: 152084 Hom.: 49570 Cov.: 34

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.829

GnomAD4 exome AF: 0.807 AC: 431 AN: 534 Hom.: 174 Cov.: 0 AF XY: 0.805 AC XY: 248 AN XY: 308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.867

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.806 AC: 122646 AN: 152202 Hom.: 49604 Cov.: 34 AF XY: 0.803 AC XY: 59787 AN XY: 74410

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.841

Gnomad4 OTH AF: 0.826

Alfa AF: 0.840 Hom.: 51068

Bravo AF: 0.807

Asia WGS AF: 0.814 AC: 2829 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.92

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

Other links and lift over

dbSNP: rs465646; hg19: chr6-111620758; COSMIC: COSV62622644; COSMIC: COSV62622644;