12-54183651-T-A

Position:

• chr12-54183651-T-A

Variant summary

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

The NM_001243787.2(SMUG1):​c.285+5A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMUG1 NM_001243787.2 splice_region, intron
• Scores: Splicing: ADA: 0.0004193
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.472

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]

SMUG1 (HGNC:):

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/exons	MANE	Protein	UniProt
SMUG1	NM_001243787.2	c.285+5A>T		splice_region_variant, intron_variant		ENST00000682136.1	NP_001230716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMUG1	ENST00000682136.1	c.285+5A>T		splice_region_variant, intron_variant			NM_001243787.2	ENSP00000507590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.95
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.011
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.95	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.12
Sift	Benign	0.052	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.44
MutPred		0.52		Gain of catalytic residue at V96 (P = 0);
MVP		0.66
ClinPred		0.11	T
GERP RS		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00042
dbscSNV1_RF	Benign	0.15
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

LitVar

Other links and lift over

dbSNP: rs193921126; hg19: chr12-54577435; COSMIC: COSV54540102; COSMIC: COSV54540102;