rs140829672

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_080911.3(UNG):c.392C>T(p.Pro131Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

UNG
NM_080911.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.28

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030479461).

BP6

Variant 12-109099241-C-T is Benign according to our data. Variant chr12-109099241-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 581300.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00065 (99/152304) while in subpopulation AFR AF= 0.00231 (96/41562). AF 95% confidence interval is 0.00194. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 99 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNG	NM_080911.3 linkuse as main transcript	c.392C>T	p.Pro131Leu	missense_variant	3/7	ENST00000242576.7
UNG	NM_003362.4 linkuse as main transcript	c.365C>T	p.Pro122Leu	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNG	ENST00000242576.7 linkuse as main transcript	c.392C>T	p.Pro131Leu	missense_variant	3/7	1	NM_080911.3	P1	P13051-1

Frequencies

GnomAD3 genomes

AF:

0.000651

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000107

AC:

AN:

251464

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461768

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000650

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00231

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.140

Hom.:

3198

Bravo

AF:

0.000725

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hyper-IgM syndrome type 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Benign

0.90

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.060

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.21

Sift

Benign

0.25

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0030

B;.

Vest4

0.32

MVP

0.88

MPC

0.13

ClinPred

0.052

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.45

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over