dbSNP rs547497060: SMUG1:p.Arg66Leu (chr12-54183744-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001243787.2(SMUG1):c.197G>T(p.Arg66Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R66H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SMUG1
NM_001243787.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.882

Publications

0 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: 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=0.19210255).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
SMUG1	NM_001243787.2	MANE Select	c.197G>T	p.Arg66Leu	missense	Exon 3 of 4	NP_001230716.1	Q53HV7-1
SMUG1	NM_001243788.2		c.197G>T	p.Arg66Leu	missense	Exon 2 of 3	NP_001230717.1	Q53HV7-1
SMUG1	NM_001351242.2		c.197G>T	p.Arg66Leu	missense	Exon 3 of 4	NP_001338171.1	Q53HV7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMUG1	ENST00000682136.1	MANE Select	c.197G>T	p.Arg66Leu	missense	Exon 3 of 4	ENSP00000507590.1	Q53HV7-1
SMUG1	ENST00000243112.9	TSL:1	c.197G>T	p.Arg66Leu	missense	Exon 2 of 4	ENSP00000243112.5	Q53HV7-2
SMUG1	ENST00000513838.5	TSL:1	c.197G>T	p.Arg66Leu	missense	Exon 4 of 6	ENSP00000423629.1	Q53HV7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111954

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.61

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.015

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

PhyloP100

0.88

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.097

Sift

Benign

0.25

Sift4G

Benign

0.28

Polyphen

0.89

Vest4

0.45

MutPred

0.29

Gain of catalytic residue at R71 (P = 2e-04)

MVP

0.62

MPC

0.36

ClinPred

0.88

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.75

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over