6-111433111-G-A

Variant names:

• chr6-111433111-G-A
• rs9487643
• NM_001372078.1:c.140-16639C>T

Variant summary

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

The NM_001372078.1(REV3L):​c.140-16639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,138 control chromosomes in the GnomAD database, including 61,734 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 0.90 (61734 hom., cov: 32)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	NM_001372078.1	MANE Select	c.140-16639C>T		intron	N/A	NP_001359007.1
	REV3L	NM_002912.5		c.140-16639C>T		intron	N/A	NP_002903.3
	REV3L	NM_001286431.2		c.-95-16639C>T		intron	N/A	NP_001273360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REV3L	ENST00000368802.8	TSL:1 MANE Select	c.140-16639C>T		intron	N/A	ENSP00000357792.3
	REV3L	ENST00000358835.7	TSL:5	c.140-16639C>T		intron	N/A	ENSP00000351697.3
	REV3L	ENST00000435970.5	TSL:2	c.-95-16639C>T		intron	N/A	ENSP00000402003.1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136813 AN: 152020 Hom.: 61671 Cov.: 32

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.900 AC: 136934 AN: 152138 Hom.: 61734 Cov.: 32 AF XY: 0.897 AC XY: 66687 AN XY: 74358

African (AFR) AF: 0.932 AC: 38713 AN: 41526

American (AMR) AF: 0.925 AC: 14162 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3183 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4738 AN: 5172

South Asian (SAS) AF: 0.917 AC: 4414 AN: 4814

European-Finnish (FIN) AF: 0.812 AC: 8547 AN: 10532

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60230 AN: 68000

Other (OTH) AF: 0.909 AC: 1919 AN: 2112

Alfa AF: 0.894 Hom.: 151936

Bravo AF: 0.910

Asia WGS AF: 0.929 AC: 3216 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		-0.83
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: rs9487643; hg19: chr6-111754314;