rs193921126

Variant names:

• chr12-54183651-T-A
• rs193921126
• NM_001243787.2:c.285+5A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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.285+5A>T		splice_region intron	N/A	NP_001230716.1	Q53HV7-1
	SMUG1	NM_001243788.2		c.285+5A>T		splice_region intron	N/A	NP_001230717.1	Q53HV7-1
	SMUG1	NM_001351242.2		c.285+5A>T		splice_region intron	N/A	NP_001338171.1	Q53HV7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMUG1	ENST00000682136.1	MANE Select	c.285+5A>T		splice_region intron	N/A	ENSP00000507590.1	Q53HV7-1
	SMUG1	ENST00000243112.9	TSL:1	c.285+5A>T		splice_region intron	N/A	ENSP00000243112.5	Q53HV7-2
	SMUG1	ENST00000513838.5	TSL:1	c.285+5A>T		splice_region intron	N/A	ENSP00000423629.1	Q53HV7-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
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
PhyloP100		0.47
PROVEAN	Benign	1.1	N
REVEL	Benign	0.12
Sift	Benign	0.052	T
Sift4G	Uncertain	0.0060	D
Mutation Taster		=83/17	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193921126;

hg19: chr12-54577435;

COSMIC: COSV54540102;

COSMIC: COSV54540102;