rs2569987

Variant names:

• chr12-109103366-T-C
• rs2569987
• NM_080911.3:c.623-67T>C

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69
• Publications: 18 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=-0.9).
• BP6: Variant 12-109103366-T-C is Benign according to our data. Variant chr12-109103366-T-C is described in ClinVar as Benign. ClinVar VariationId is 1230454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
UNG	NM_080911.3	c.623-67T>C		intron_variant	Intron 5 of 6	ENST00000242576.7	NP_550433.1
UNG	NM_003362.4	c.596-67T>C		intron_variant	Intron 4 of 5		NP_003353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNG	ENST00000242576.7	c.623-67T>C		intron_variant	Intron 5 of 6	1	NM_080911.3	ENSP00000242576.3

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

African (AFR) AF: 0.0405 AC: 1218 AN: 30088

American (AMR) AF: 0.0816 AC: 3547 AN: 43494

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2531 AN: 24936

East Asian (EAS) AF: 0.000515 AC: 20 AN: 38858

South Asian (SAS) AF: 0.0667 AC: 5431 AN: 81470

European-Finnish (FIN) AF: 0.140 AC: 7417 AN: 52986

Middle Eastern (MID) AF: 0.0918 AC: 485 AN: 5282

European-Non Finnish (NFE) AF: 0.173 AC: 165306 AN: 956374

Other (OTH) AF: 0.128 AC: 7007 AN: 54720

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

African (AFR) AF: 0.0452 AC: 1877 AN: 41562

American (AMR) AF: 0.0962 AC: 1470 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0988 AC: 343 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0552 AC: 266 AN: 4822

European-Finnish (FIN) AF: 0.143 AC: 1511 AN: 10590

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11618 AN: 68006

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.139 Hom.: 1654

Bravo AF: 0.110

Asia WGS AF: 0.0270 AC: 95 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

- -

Oct 24, 2018

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	-0.90
CADD	Benign	0.41
DANN	Benign	0.66
PhyloP100		-1.7
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: rs2569987; hg19: chr12-109541171;