NM_001243787.2:c.410G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243787.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMUG1	NM_001243787.2	MANE Select	c.410G>C	p.Ser137Thr	missense	Exon 4 of 4	NP_001230716.1	Q53HV7-1
	SMUG1	NM_001243788.2		c.410G>C	p.Ser137Thr	missense	Exon 3 of 3	NP_001230717.1	Q53HV7-1
	SMUG1	NM_001351242.2		c.410G>C	p.Ser137Thr	missense	Exon 4 of 4	NP_001338171.1	Q53HV7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMUG1	ENST00000682136.1	MANE Select	c.410G>C	p.Ser137Thr	missense	Exon 4 of 4	ENSP00000507590.1	Q53HV7-1
	SMUG1	ENST00000243112.9	TSL:1	c.405+5G>C		splice_region intron	N/A	ENSP00000243112.5	Q53HV7-2
	SMUG1	ENST00000513838.5	TSL:1	c.405+5G>C		splice_region intron	N/A	ENSP00000423629.1	Q53HV7-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.65		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
Mutation Taster		=6/94	disease causing

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

Other links and lift over

hg19: chr12-54576283;