12-54183836-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001243787.2(SMUG1):c.105G>T(p.Glu35Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
SMUG1
NM_001243787.2 missense
NM_001243787.2 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 0.685
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 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22510907).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMUG1 | NM_001243787.2 | c.105G>T | p.Glu35Asp | missense_variant | 3/4 | ENST00000682136.1 | NP_001230716.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMUG1 | ENST00000682136.1 | c.105G>T | p.Glu35Asp | missense_variant | 3/4 | NM_001243787.2 | ENSP00000507590.1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250326Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135344
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461568Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727064
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 10, 2022 | The c.105G>T (p.E35D) 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 105, causing the glutamic acid (E) at amino acid position 35 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;T;.;T;.;T;.;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;.;.;.;D;.;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M;.;M;M;M;.;.;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;T;D;D;D;T;D;T;D;T;D;D;D;T
Sift4G
Uncertain
D;T;D;D;T;T;D;T;D;.;T;.;.;D
Polyphen
D;D;D;D;D;D;D;D;.;.;.;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);Loss of disorder (P = 0.084);
MVP
MPC
0.82
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at