chr12-109101994-G-A

Position:

• chr12-109101994-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_080911.3(UNG):​c.528G>A​(p.Pro176Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000873 in 1,613,808 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00046 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00092 (16 hom.)
• Consequence: UNG NM_080911.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.54

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 12-109101994-G-A is Benign according to our data. Variant chr12-109101994-G-A is described in ClinVar as [Benign]. Clinvar id is 306972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-109101994-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00046 (70/152260) while in subpopulation SAS AF= 0.0104 (50/4822). AF 95% confidence interval is 0.00808. There are 2 homozygotes in gnomad4. There are 49 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 70 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNG	NM_080911.3	c.528G>A	p.Pro176Pro	synonymous_variant	4/7	ENST00000242576.7	NP_550433.1
UNG	NM_003362.4	c.501G>A	p.Pro167Pro	synonymous_variant	3/6		NP_003353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNG	ENST00000242576.7	c.528G>A	p.Pro176Pro	synonymous_variant	4/7	1	NM_080911.3	ENSP00000242576.3

Frequencies

GnomAD3 genomes AF: 0.000454 AC: 69 AN: 152142 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00175 AC: 439 AN: 251452 Hom.: 6 AF XY: 0.00230 AC XY: 313 AN XY: 135902

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0132

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.000916 AC: 1339 AN: 1461548 Hom.: 16 Cov.: 31 AF XY: 0.00127 AC XY: 924 AN XY: 727072

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000133

Gnomad4 OTH exome AF: 0.000961

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152260 Hom.: 2 Cov.: 31 AF XY: 0.000658 AC XY: 49 AN XY: 74440

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000244 Hom.: 0

Bravo AF: 0.000212

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hyper-IgM syndrome type 5 Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

UNG: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.3
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs373915335; hg19: chr12-109539799;