12-54182385-C-A

Variant summary

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

The NM_001243787.2(SMUG1):​c.524G>T​(p.Arg175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SMUG1
NM_001243787.2 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10
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]

Genome browser will be placed here

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.524G>T p.Arg175Leu 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.524G>T p.Arg175Leu missense_variant Exon 4 of 4 NM_001243787.2 ENSP00000507590.1 Q53HV7-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251222
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000493
AC:
72
AN:
1461892
Hom.:
0
Cov.:
33
AF XY:
0.0000523
AC XY:
38
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000450
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000675
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.524G>T (p.R175L) 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 524, causing the arginine (R) at amino acid position 175 to be replaced by a leucine (L). 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
Pathogenic
0.64
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.36
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T;T;T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.93
.;.;D
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.44
T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.3
M;M;M
PrimateAI
Uncertain
0.48
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Benign
0.20
Sift
Benign
0.046
D;D;D
Sift4G
Uncertain
0.020
D;D;D
Polyphen
0.97
D;D;D
Vest4
0.28
MutPred
0.52
Gain of catalytic residue at A171 (P = 0.0039);Gain of catalytic residue at A171 (P = 0.0039);Gain of catalytic residue at A171 (P = 0.0039);
MVP
0.66
MPC
0.72
ClinPred
0.90
D
GERP RS
3.0
Varity_R
0.22
gMVP
0.63

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs541683930; hg19: chr12-54576169; API