chr12-54182452-C-T

Variant names:

• chr12-54182452-C-T
• NM_001243787.2:c.457G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001243787.2(SMUG1):​c.457G>A​(p.Glu153Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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: 2.75
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15441006).

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.457G>A	p.Glu153Lys	missense	Exon 4 of 4	NP_001230716.1	Q53HV7-1
	SMUG1	NM_001243788.2		c.457G>A	p.Glu153Lys	missense	Exon 3 of 3	NP_001230717.1	Q53HV7-1
	SMUG1	NM_001351242.2		c.457G>A	p.Glu153Lys	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.457G>A	p.Glu153Lys	missense	Exon 4 of 4	ENSP00000507590.1	Q53HV7-1
	SMUG1	ENST00000243112.9	TSL:1	c.405+52G>A		intron	N/A	ENSP00000243112.5	Q53HV7-2
	SMUG1	ENST00000513838.5	TSL:1	c.405+52G>A		intron	N/A	ENSP00000423629.1	Q53HV7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.7
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.10
Sift	Benign	0.13	T
Sift4G	Benign	0.064	T
Polyphen		0.062	B
Vest4		0.25
MutPred		0.51		Gain of catalytic residue at H157 (P = 0.0011)
MVP		0.60
MPC		0.32
ClinPred		0.56	D
GERP RS		3.0
Varity_R		0.075
gMVP		0.55
Mutation Taster		=94/6	polymorphism

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: chr12-54576236;