Genetic Variant SMUG1:c.*334G>A (chr12-54181762-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001243787.2(SMUG1):c.*334G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0065 in 1,452,408 control chromosomes in the GnomAD database, including 539 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.033 ( 294 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 245 hom. )

Consequence

SMUG1
NM_001243787.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.470

Publications

3 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMUG1	NM_001243787.2	MANE Select	c.*334G>A	3_prime_UTR	Exon 4 of 4	NP_001230716.1
SMUG1	NM_001243788.2		c.*334G>A	3_prime_UTR	Exon 3 of 3	NP_001230717.1
SMUG1	NM_001351242.2		c.*334G>A	3_prime_UTR	Exon 4 of 4	NP_001338171.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SMUG1	ENST00000682136.1	MANE Select	c.*334G>A	3_prime_UTR	Exon 4 of 4	ENSP00000507590.1
SMUG1	ENST00000243112.9	TSL:1	c.406-115G>A	intron	N/A	ENSP00000243112.5
SMUG1	ENST00000513838.5	TSL:1	c.406-115G>A	intron	N/A	ENSP00000423629.1

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5004

AN:

152174

Hom.:

293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.0272

GnomAD4 exome

AF:

0.00340

AC:

4414

AN:

1300116

Hom.:

245

Cov.:

AF XY:

0.00299

AC XY:

1894

AN XY:

632628

show subpopulations

African (AFR)

AF:

0.118

AC:

3424

AN:

28926

American (AMR)

AF:

0.00876

AC:

205

AN:

23396

Ashkenazi Jewish (ASJ)

AF:

0.00160

AC:

AN:

20010

East Asian (EAS)

AF:

0.00

AC:

AN:

35058

South Asian (SAS)

AF:

0.000423

AC:

AN:

63788

European-Finnish (FIN)

AF:

0.000194

AC:

AN:

30926

Middle Eastern (MID)

AF:

0.00710

AC:

AN:

4790

European-Non Finnish (NFE)

AF:

0.000224

AC:

233

AN:

1038920

Other (OTH)

AF:

0.00834

AC:

453

AN:

54302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

179

358

536

715

894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0330

AC:

5023

AN:

152292

Hom.:

294

Cov.:

AF XY:

0.0317

AC XY:

2357

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.114

AC:

4725

AN:

41538

American (AMR)

AF:

0.0127

AC:

195

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000514

AC:

AN:

68034

Other (OTH)

AF:

0.0270

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

233

466

699

932

1165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0222

Hom.:

Bravo

AF:

0.0374

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.5

(source)

DANN

Benign

0.48

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over