Variant 12-54183916-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001243787.2(SMUG1):c.25T>C(p.Ser9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMUG1
NM_001243787.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.122

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027233481).

BP6

Variant 12-54183916-A-G is Benign according to our data. Variant chr12-54183916-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2622276.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMUG1	NM_001243787.2 linkuse as main transcript	c.25T>C	p.Ser9Pro	missense_variant	3/4	ENST00000682136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMUG1	ENST00000682136.1 linkuse as main transcript	c.25T>C	p.Ser9Pro	missense_variant	3/4		NM_001243787.2	P1	Q53HV7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1434740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710692

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 12, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.48

DANN

Benign

0.059

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0054

M_CAP

Benign

0.0030

MetaRNN

Benign

0.027

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.97

N;N;N;N;.;N;N;N;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.62

N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.31

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

Sift4G

Benign

0.22

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

Polyphen

0.0

B;B;B;B;B;B;B;B;.;.;.;.;.;.

Vest4

0.057

MutPred

0.24

Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);Gain of catalytic residue at A14 (P = 0.001);

MVP

0.17

MPC

0.30

ClinPred

0.049

GERP RS

-0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.045

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over