12-54182121-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001243787.2(SMUG1):​c.788G>T​(p.Gly263Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SMUG1
NM_001243787.2 missense

Scores

3
14
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40
Variant links:
Genes affected
SMUG1 (HGNC:17148): (single-strand-selective monofunctional uracil-DNA glycosylase 1) This gene encodes a protein that participates in base excision repair by removing uracil from single- and double-stranded DNA. Many alternatively spliced transcript variants exist for this gene; the full-length nature is known for some but not all of the variants. [provided by RefSeq, Aug 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SMUG1NM_001243787.2 linkc.788G>T p.Gly263Val missense_variant Exon 4 of 4 ENST00000682136.1 NP_001230716.1 Q53HV7-1A0A024RAZ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMUG1ENST00000682136.1 linkc.788G>T p.Gly263Val missense_variant Exon 4 of 4 NM_001243787.2 ENSP00000507590.1 Q53HV7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.788G>T (p.G263V) alteration is located in exon 1 (coding exon 1) of the SMUG1 gene. This alteration results from a G to T substitution at nucleotide position 788, causing the glycine (G) at amino acid position 263 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.51
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T;T;T;.
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.57
.;.;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Uncertain
-0.19
T
MutationAssessor
Uncertain
2.9
M;M;M;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-7.4
D;D;D;N
REVEL
Uncertain
0.41
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
1.0
D;D;D;.
Vest4
0.53
MutPred
0.51
Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);.;
MVP
0.85
MPC
0.29
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.88
gMVP
0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-54575905; API