chr12-54183916-A-G

Variant names:

• chr12-54183916-A-G
• NM_001243787.2:c.25T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.122

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

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 rank	MANE	Protein	UniProt
SMUG1	NM_001243787.2	c.25T>C	p.Ser9Pro	missense_variant	Exon 3 of 4	ENST00000682136.1	NP_001230716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMUG1	ENST00000682136.1	c.25T>C	p.Ser9Pro	missense_variant	Exon 3 of 4		NM_001243787.2	ENSP00000507590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1434740 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 12, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.48
DANN	Benign	0.059
DEOGEN2	Benign	0.045	.;T;.;.;.;T;.;T;.;T;.;.;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.57	.;.;.;.;T;.;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.027	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N;N;N;N;.;N;N;N;.;.;.;.;.;.
PrimateAI	Benign	0.39	T
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	T
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.

Other links and lift over

hg19: chr12-54577700;