12-54181674-T-C

Position:

• chr12-54181674-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243787.2(SMUG1):​c.*422A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,582,274 control chromosomes in the GnomAD database, including 368,207 homozygotes. 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 0.70 (38143 hom., cov: 32)
  • Exomes 𝑓: 0.68 (330064 hom.)
• Consequence: SMUG1 NM_001243787.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMUG1	NM_001243787.2	c.*422A>G		3_prime_UTR_variant	4/4	ENST00000682136.1	NP_001230716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMUG1	ENST00000682136.1	c.*422A>G		3_prime_UTR_variant	4/4		NM_001243787.2	ENSP00000507590	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107097 AN: 151980 Hom.: 38114 Cov.: 32

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.716

GnomAD3 exomes AF: 0.669 AC: 139779 AN: 209044 Hom.: 47445 AF XY: 0.677 AC XY: 77486 AN XY: 114432

Gnomad AFR exome AF: 0.803

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.682

Gnomad EAS exome AF: 0.642

Gnomad SAS exome AF: 0.793

Gnomad FIN exome AF: 0.705

Gnomad NFE exome AF: 0.665

Gnomad OTH exome AF: 0.679

GnomAD4 exome AF: 0.677 AC: 968844 AN: 1430176 Hom.: 330064 Cov.: 38 AF XY: 0.680 AC XY: 482737 AN XY: 709822

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.531

Gnomad4 ASJ exome AF: 0.677

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.792

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.670

Gnomad4 OTH exome AF: 0.693

GnomAD4 genome AF: 0.705 AC: 107174 AN: 152098 Hom.: 38143 Cov.: 32 AF XY: 0.707 AC XY: 52582 AN XY: 74336

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.712

Alfa AF: 0.669 Hom.: 35915

Bravo AF: 0.697

Asia WGS AF: 0.721 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.26
BranchPoint Hunter		0.0

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

LitVar

Other links and lift over

dbSNP: rs971; hg19: chr12-54575458;