Genetic Variant NM_080911.3:c.534-25dupT (chr12-109102808-G-GT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.40

Publications

6 publications found

Variant links:

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

UNG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNG	NM_080911.3 link	c.534-25dupT		intron_variant	Intron 4 of 6	ENST00000242576.7	NP_550433.1	P13051-1E5KTA5
UNG	NM_003362.4 link	c.507-25dupT		intron_variant	Intron 3 of 5		NP_003353.1	P13051-2E5KTA6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNG	ENST00000242576.7 link	c.534-31_534-30insT		intron_variant	Intron 4 of 6	1	NM_080911.3	ENSP00000242576.3		P13051-1

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28859

AN:

151846

Hom.:

2746

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.193

AC XY:

134777

AN XY:

698908

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

10513

21026

31540

42053

52566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6634

13268

19902

26536

33170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.190

AC:

28864

AN:

151964

Hom.:

2748

Cov.:

AF XY:

0.193

AC XY:

14311

AN XY:

74242

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12547

AN:

67942

Other (OTH)

AF:

0.179

AC:

378

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1189

2377

3566

4754

5943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.189

Hom.:

501

Bravo

AF:

0.184

Asia WGS

AF:

0.267

AC:

929

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.4

BranchPoint Hunter

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over