rs2569987

chr12-109103366-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_080911.3(UNG):c.623-67T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,440,434 control chromosomes in the GnomAD database, including 17,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1315 hom., cov: 31)
  • Exomes 𝑓: 0.15 (16065 hom.)
• Consequence: UNG NM_080911.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.69

Genes affected

UNG (HGNC:12572): (uracil DNA glycosylase) This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-109103366-T-C is Benign according to our data. Variant chr12-109103366-T-C is described in ClinVar as [Benign]. Clinvar id is 1230454.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNG	NM_080911.3	c.623-67T>C		intron_variant		ENST00000242576.7
UNG	NM_003362.4	c.596-67T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNG	ENST00000242576.7	c.623-67T>C		intron_variant		1	NM_080911.3	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17527 AN: 152108 Hom.: 1315 Cov.: 31

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0547

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.150 AC: 192962 AN: 1288208 Hom.: 16065 AF XY: 0.147 AC XY: 95549 AN XY: 649242

Gnomad4 AFR exome AF: 0.0405

Gnomad4 AMR exome AF: 0.0816

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000515

Gnomad4 SAS exome AF: 0.0667

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.115 AC: 17529 AN: 152226 Hom.: 1315 Cov.: 31 AF XY: 0.112 AC XY: 8305 AN XY: 74410

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.0962

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0552

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.105

Alfa AF: 0.152 Hom.: 1249

Bravo AF: 0.110

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.41
Dann	Benign	0.66

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: rs2569987; hg19: chr12-109541171;