12-109102808-GT-GTT

Variant names:

• chr12-109102808-G-GT
• rs3219235
• NM_080911.3:c.534-25dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_080911.3(UNG):​c.534-25dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,548,134 control chromosomes in the GnomAD database, including 29,381 homozygotes. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.19 (2748 hom., cov: 27)
  • Exomes 𝑓: 0.19 (26633 hom.)
• Consequence: UNG NM_080911.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.40
• Publications: 6 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 -16 ACMG points.

• BP6: Variant 12-109102808-G-GT is Benign according to our data. Variant chr12-109102808-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1249431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080911.3. 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
	UNG	NM_080911.3	MANE Select	c.534-25dupT		intron	N/A	NP_550433.1	E5KTA5
	UNG	NM_003362.4		c.507-25dupT		intron	N/A	NP_003353.1	P13051-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNG	ENST00000242576.7	TSL:1 MANE Select	c.534-31_534-30insT		intron	N/A	ENSP00000242576.3	P13051-1
	UNG	ENST00000336865.6	TSL:1	c.507-31_507-30insT		intron	N/A	ENSP00000337398.2	P13051-2
	UNG	ENST00000446767.2	TSL:1	n.409-31_409-30insT		intron	N/A	ENSP00000400287.2	Q68DM5

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28859 AN: 151846 Hom.: 2746 Cov.: 27

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.208 AC: 52010 AN: 250470 AF XY: 0.211

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.340

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.186

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.190 AC: 265847 AN: 1396170 Hom.: 26633 Cov.: 26 AF XY: 0.193 AC XY: 134777 AN XY: 698908

African (AFR) AF: 0.166 AC: 5344 AN: 32156

American (AMR) AF: 0.163 AC: 7267 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6128 AN: 25650

East Asian (EAS) AF: 0.312 AC: 12276 AN: 39374

South Asian (SAS) AF: 0.266 AC: 22602 AN: 84836

European-Finnish (FIN) AF: 0.197 AC: 10373 AN: 52764

Middle Eastern (MID) AF: 0.153 AC: 862 AN: 5650

European-Non Finnish (NFE) AF: 0.180 AC: 189660 AN: 1052974

Other (OTH) AF: 0.195 AC: 11335 AN: 58150

GnomAD4 genome AF: 0.190 AC: 28864 AN: 151964 Hom.: 2748 Cov.: 27 AF XY: 0.193 AC XY: 14311 AN XY: 74242

African (AFR) AF: 0.171 AC: 7073 AN: 41434

American (AMR) AF: 0.180 AC: 2746 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1667 AN: 5166

South Asian (SAS) AF: 0.272 AC: 1306 AN: 4806

European-Finnish (FIN) AF: 0.201 AC: 2119 AN: 10552

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12547 AN: 67942

Other (OTH) AF: 0.179 AC: 378 AN: 2108

Alfa AF: 0.189 Hom.: 501

Bravo AF: 0.184

Asia WGS AF: 0.267 AC: 929 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4
BranchPoint Hunter		2.0
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: rs3219235; hg19: chr12-109540613; COSMIC: COSV107286520; COSMIC: COSV107286520;