12-109098052-T-A

Variant names:

• chr12-109098052-T-A
• rs1018783
• NM_080911.3:c.132+241T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080911.3(UNG):​c.132+241T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,368,336 control chromosomes in the GnomAD database, including 24,297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4665 hom., cov: 33)
  • Exomes 𝑓: 0.17 (19632 hom.)
• Consequence: UNG NM_080911.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.503
• Publications: 7 publications found

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]

UNG Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 5

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-109098052-T-A is Benign according to our data. Variant chr12-109098052-T-A is described in ClinVar as Benign. ClinVar VariationId is 1258409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNG	NM_080911.3	c.132+241T>A		intron_variant	Intron 1 of 6	ENST00000242576.7	NP_550433.1
UNG	NM_003362.4	c.-275T>A		upstream_gene_variant			NP_003353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNG	ENST00000242576.7	c.132+241T>A		intron_variant	Intron 1 of 6	1	NM_080911.3	ENSP00000242576.3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34456 AN: 151714 Hom.: 4662 Cov.: 33

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0489

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.174 AC: 212036 AN: 1216504 Hom.: 19632 AF XY: 0.173 AC XY: 101635 AN XY: 586544

African (AFR) AF: 0.382 AC: 9793 AN: 25660

American (AMR) AF: 0.148 AC: 2479 AN: 16768

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 2556 AN: 17556

East Asian (EAS) AF: 0.0577 AC: 1834 AN: 31810

South Asian (SAS) AF: 0.132 AC: 7005 AN: 53056

European-Finnish (FIN) AF: 0.172 AC: 4924 AN: 28548

Middle Eastern (MID) AF: 0.160 AC: 543 AN: 3398

European-Non Finnish (NFE) AF: 0.176 AC: 174067 AN: 989244

Other (OTH) AF: 0.175 AC: 8835 AN: 50464

GnomAD4 genome AF: 0.227 AC: 34486 AN: 151832 Hom.: 4665 Cov.: 33 AF XY: 0.223 AC XY: 16565 AN XY: 74250

African (AFR) AF: 0.383 AC: 15864 AN: 41398

American (AMR) AF: 0.162 AC: 2468 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3468

East Asian (EAS) AF: 0.0488 AC: 250 AN: 5126

South Asian (SAS) AF: 0.140 AC: 673 AN: 4814

European-Finnish (FIN) AF: 0.182 AC: 1911 AN: 10522

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12112 AN: 67918

Other (OTH) AF: 0.228 AC: 480 AN: 2102

Alfa AF: 0.203 Hom.: 495

Bravo AF: 0.231

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.8
DANN	Benign	0.71
PhyloP100		0.50
PromoterAI		-0.017	Neutral
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: rs1018783; hg19: chr12-109535857;