12-54182452-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMUG1	NM_001243787.2	c.457G>A	p.Glu153Lys	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.457G>A	p.Glu153Lys	missense_variant	Exon 4 of 4		NM_001243787.2	ENSP00000507590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.457G>A (p.E153K) alteration is located in exon 1 (coding exon 1) of the SMUG1 gene. This alteration results from a G to A substitution at nucleotide position 457, causing the glutamic acid (E) at amino acid position 153 to be replaced by a lysine (K). 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	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;T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.91	.;.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L;L;L;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.10
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.064	T;T;T;.
Polyphen		0.062	B;B;B;.
Vest4		0.25
MutPred		0.51		Gain of catalytic residue at H157 (P = 0.0011);Gain of catalytic residue at H157 (P = 0.0011);Gain of catalytic residue at H157 (P = 0.0011);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

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: chr12-54576236;