12-54182499-C-G

Variant names:

• chr12-54182499-C-G
• NM_001243787.2:c.410G>C

Variant summary

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

The NM_001243787.2(SMUG1):​c.410G>C​(p.Ser137Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMUG1 NM_001243787.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

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]

ACMG classification

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
SMUG1	NM_001243787.2	c.410G>C	p.Ser137Thr	missense_variant	Exon 4 of 4	ENST00000682136.1	NP_001230716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMUG1	ENST00000682136.1	c.410G>C	p.Ser137Thr	missense_variant	Exon 4 of 4		NM_001243787.2	ENSP00000507590.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.410G>C (p.S137T) alteration is located in exon 1 (coding exon 1) of the SMUG1 gene. This alteration results from a G to C substitution at nucleotide position 410, causing the serine (S) at amino acid position 137 to be replaced by a threonine (T). 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	0.80
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T;T;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	.;.;D;D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.1	M;M;M;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;.
Polyphen		1.0	D;D;D;.
Vest4		0.79
MutPred		0.65		Gain of catalytic residue at V136 (P = 0.0014);Gain of catalytic residue at V136 (P = 0.0014);Gain of catalytic residue at V136 (P = 0.0014);Gain of catalytic residue at V136 (P = 0.0014);
MVP		0.89
MPC		0.63
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.81
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-54576283;