12-54182121-C-A

Variant names:

• chr12-54182121-C-A
• NM_001243787.2:c.788G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• 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.788G>T	p.Gly263Val	missense	Exon 4 of 4	NP_001230716.1	Q53HV7-1
	SMUG1	NM_001243788.2		c.788G>T	p.Gly263Val	missense	Exon 3 of 3	NP_001230717.1	Q53HV7-1
	SMUG1	NM_001351242.2		c.788G>T	p.Gly263Val	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.788G>T	p.Gly263Val	missense	Exon 4 of 4	ENSP00000507590.1	Q53HV7-1
	SMUG1	ENST00000243112.9	TSL:1	c.405+383G>T		intron	N/A	ENSP00000243112.5	Q53HV7-2
	SMUG1	ENST00000513838.5	TSL:1	c.405+383G>T		intron	N/A	ENSP00000423629.1	Q53HV7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	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
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.4
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.51		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
Mutation Taster		=17/83	disease causing

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

Other links and lift over

hg19: chr12-54575905;