6-111299555-G-A

Variant names:

• chr6-111299555-G-A
• rs465646
• ENST00000462119.5:n.1991C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000462119.5(REV3L):​n.1991C>T variant causes a non coding transcript exon 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 ENST00000462119.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43
• Publications: 29 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 (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000462119.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	NM_001372078.1	MANE Select	c.*461C>T		3_prime_UTR	Exon 32 of 32	NP_001359007.1
	REV3L	NM_002912.5		c.*461C>T		3_prime_UTR	Exon 33 of 33	NP_002903.3
	REV3L	NM_001286431.2		c.*461C>T		3_prime_UTR	Exon 35 of 35	NP_001273360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	ENST00000462119.5	TSL:1	n.1991C>T		non_coding_transcript_exon	Exon 7 of 7
	REV3L	ENST00000368802.8	TSL:1 MANE Select	c.*461C>T		3_prime_UTR	Exon 32 of 32	ENSP00000357792.3
	REV3L	ENST00000422377.5	TSL:2	n.*9838C>T		non_coding_transcript_exon	Exon 34 of 34	ENSP00000393184.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 1.00 AC: 4 AN: 4

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.792 AC: 336 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.867 AC: 78 AN: 90

Other (OTH) AF: 1.00 AC: 10 AN: 10

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

African (AFR) AF: 0.739 AC: 30672 AN: 41514

American (AMR) AF: 0.841 AC: 12866 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2956 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4154 AN: 5188

South Asian (SAS) AF: 0.781 AC: 3766 AN: 4822

European-Finnish (FIN) AF: 0.788 AC: 8332 AN: 10580

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57172 AN: 68018

Other (OTH) AF: 0.826 AC: 1743 AN: 2110

Alfa AF: 0.830 Hom.: 144526

Bravo AF: 0.807

Asia WGS AF: 0.814 AC: 2829 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.92
PhyloP100		4.4
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: rs465646; hg19: chr6-111620758; COSMIC: COSV62622644; COSMIC: COSV62622644;