rs2233920

Variant names:

• chr12-54183897-C-A
• rs2233920
• NM_001243787.2:c.44G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-54183897-C-A
• chr12-54183897-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001243787.2(SMUG1):​c.44G>T​(p.Gly15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,604,580 control chromosomes in the GnomAD database, including 164 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (83 hom.)
• Consequence: SMUG1 NM_001243787.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.238
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002324164).
• BP6: Variant 12-54183897-C-A is Benign according to our data. Variant chr12-54183897-C-A is described in ClinVar as Benign. ClinVar VariationId is 776713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMUG1	NM_001243787.2	c.44G>T	p.Gly15Val	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.44G>T	p.Gly15Val	missense_variant	Exon 3 of 4		NM_001243787.2	ENSP00000507590.1

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2500 AN: 152128 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00425 AC: 988 AN: 232400 AF XY: 0.00309

Gnomad AFR exome AF: 0.0598

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000768

Gnomad OTH exome AF: 0.00227

GnomAD4 exome AF: 0.00159 AC: 2308 AN: 1452334 Hom.: 83 Cov.: 31 AF XY: 0.00135 AC XY: 972 AN XY: 721388

African (AFR) AF: 0.0565 AC: 1886 AN: 33368

American (AMR) AF: 0.00347 AC: 150 AN: 43280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.000283 AC: 24 AN: 84950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51920

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5746

European-Non Finnish (NFE) AF: 0.0000280 AC: 31 AN: 1107716

Other (OTH) AF: 0.00341 AC: 205 AN: 60098

GnomAD4 genome AF: 0.0165 AC: 2507 AN: 152246 Hom.: 81 Cov.: 32 AF XY: 0.0157 AC XY: 1167 AN XY: 74426

African (AFR) AF: 0.0574 AC: 2385 AN: 41520

American (AMR) AF: 0.00562 AC: 86 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00422 Hom.: 6

Bravo AF: 0.0182

ESP6500AA AF: 0.0499 AC: 220

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00525 AC: 637

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.5
DANN	Benign	0.52
DEOGEN2	Benign	0.063	.;T;.;.;.;T;.;T;.;T;.;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	.;.;.;.;T;.;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0023	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;L;L;.;L;L;L;.;.;.;.;.;.
PhyloP100		0.24
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.041
Sift	Benign	0.041	D;T;D;D;D;T;D;T;D;T;T;T;T;T
Sift4G	Uncertain	0.015	D;T;D;D;D;T;D;T;D;.;T;.;.;D
Polyphen		0.69	P;B;P;P;B;B;P;B;.;.;.;.;.;.
Vest4		0.14
MVP		0.38
MPC		0.44
ClinPred		0.00028	T
GERP RS		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2233920; hg19: chr12-54577681;