rs76391872

Variant names:

• chr12-109103569-C-G
• rs76391872
• NM_080911.3:c.759C>G
• UNG p.Leu253Leu

Your query was ambiguous. Multiple possible variants found:

• chr12-109103569-C-G
• chr12-109103569-C-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BA1

The NM_080911.3(UNG):​c.759C>G​(p.Leu253Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,613,926 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (94 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (82 hom.)
• Consequence: UNG NM_080911.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.338
• Publications: 2 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.287).
• BP6: Variant 12-109103569-C-G is Benign according to our data. Variant chr12-109103569-C-G is described in ClinVar as Benign. ClinVar VariationId is 306977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.338 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0645 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.759C>G	p.Leu253Leu	synonymous	Exon 6 of 7	NP_550433.1	E5KTA5
	UNG	NM_003362.4		c.732C>G	p.Leu244Leu	synonymous	Exon 5 of 6	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.759C>G	p.Leu253Leu	synonymous	Exon 6 of 7	ENSP00000242576.3	P13051-1
	UNG	ENST00000336865.6	TSL:1	c.732C>G	p.Leu244Leu	synonymous	Exon 5 of 6	ENSP00000337398.2	P13051-2
	UNG	ENST00000446767.2	TSL:1	n.*208C>G		non_coding_transcript_exon	Exon 4 of 5	ENSP00000400287.2	Q68DM5

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2866 AN: 152072 Hom.: 94 Cov.: 31

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00456 AC: 1147 AN: 251346 AF XY: 0.00321

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00180 AC: 2631 AN: 1461736 Hom.: 82 Cov.: 32 AF XY: 0.00153 AC XY: 1110 AN XY: 727164

African (AFR) AF: 0.0655 AC: 2194 AN: 33476

American (AMR) AF: 0.00320 AC: 143 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00318 AC: 18 AN: 5662

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1112006

Other (OTH) AF: 0.00339 AC: 205 AN: 60386

GnomAD4 genome AF: 0.0189 AC: 2873 AN: 152190 Hom.: 94 Cov.: 31 AF XY: 0.0176 AC XY: 1313 AN XY: 74400

African (AFR) AF: 0.0665 AC: 2761 AN: 41492

American (AMR) AF: 0.00484 AC: 74 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68014

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00582 Hom.: 7

Bravo AF: 0.0206

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hyper-IgM syndrome type 5 (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.9
DANN	Benign	0.75
PhyloP100		0.34
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs76391872;

hg19: chr12-109541374;