rs17511504

Variant names:

• chr6-111309324-G-A
• rs17511504
• NM_001372078.1:c.9042+529C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001372078.1(REV3L):​c.9042+529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 152,386 control chromosomes in the GnomAD database, including 53 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 0.022 (53 hom., cov: 31)
  • Exomes 𝑓: 0.027 (0 hom.)
• Consequence: REV3L NM_001372078.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 4 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]

ENSG00000272356 (HGNC:58340):

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=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0219 (3333/152086) while in subpopulation NFE AF = 0.0324 (2203/67958). AF 95% confidence interval is 0.0313. There are 53 homozygotes in GnomAd4. There are 1596 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3333 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.9042+529C>T		intron	N/A	NP_001359007.1	O60673-1
	REV3L	NM_002912.5		c.9042+529C>T		intron	N/A	NP_002903.3	O60673-1
	REV3L	NM_001286431.2		c.8808+529C>T		intron	N/A	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.9042+529C>T		intron	N/A	ENSP00000357792.3	O60673-1
	REV3L	ENST00000462119.5	TSL:1	n.947+529C>T		intron	N/A
	REV3L	ENST00000358835.7	TSL:5	c.9042+529C>T		intron	N/A	ENSP00000351697.3	O60673-1

Frequencies

GnomAD3 genomes AF: 0.0219 AC: 3334 AN: 151968 Hom.: 53 Cov.: 31

Gnomad AFR AF: 0.00606

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00500

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.0307

GnomAD4 exome AF: 0.0267 AC: 8 AN: 300 Hom.: 0 Cov.: 0 AF XY: 0.0194 AC XY: 4 AN XY: 206

African (AFR) AF: 0.0714 AC: 1 AN: 14

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0240 AC: 6 AN: 250

Other (OTH) AF: 0.0625 AC: 1 AN: 16

GnomAD4 genome AF: 0.0219 AC: 3333 AN: 152086 Hom.: 53 Cov.: 31 AF XY: 0.0215 AC XY: 1596 AN XY: 74358

African (AFR) AF: 0.00604 AC: 251 AN: 41522

American (AMR) AF: 0.0307 AC: 469 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00500 AC: 24 AN: 4798

European-Finnish (FIN) AF: 0.0181 AC: 192 AN: 10594

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0324 AC: 2203 AN: 67958

Other (OTH) AF: 0.0303 AC: 64 AN: 2110

Alfa AF: 0.0258 Hom.: 10

Bravo AF: 0.0238

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.82
PhyloP100		0.25
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: rs17511504; hg19: chr6-111630527;