Genetic Variant SMUG1:p.Arg71Leu (chr12-54183729-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001243787.2(SMUG1):c.212G>T(p.Arg71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Consequence

SMUG1
NM_001243787.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35298738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMUG1	NM_001243787.2 link	c.212G>T	p.Arg71Leu	missense_variant	Exon 3 of 4	ENST00000682136.1	NP_001230716.1	Q53HV7-1A0A024RAZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMUG1	ENST00000682136.1 link	c.212G>T	p.Arg71Leu	missense_variant	Exon 3 of 4		NM_001243787.2	ENSP00000507590.1		Q53HV7-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251290

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T;.;.;.;T;.;T;.;T;.;.;T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.91

.;.;.;.;D;.;D;D;D;D;D;D;D;D

M_CAP

Benign

0.074

MetaRNN

Benign

0.35

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.3

M;M;M;M;.;M;M;M;.;.;.;.;.;.

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.0

D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.13

Sift

Uncertain

0.013

D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D;D;D;D;D;.;D;.;.;D

Polyphen

0.80

P;P;P;P;D;P;P;P;.;.;.;.;.;.

Vest4

0.56

MutPred

0.58

Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);Gain of catalytic residue at Q74 (P = 0.0015);

MVP

0.82

MPC

0.71

ClinPred

0.89

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over