12-54187830-T-C

Position:

• chr12-54187830-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.-31A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,614 control chromosomes in the GnomAD database, including 17,724 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 0.47 (17724 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: SMUG1 NM_001243787.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.955

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMUG1	NM_001243787.2	c.-31A>G		5_prime_UTR_variant	2/4	ENST00000682136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMUG1	ENST00000682136.1	c.-31A>G		5_prime_UTR_variant	2/4		NM_001243787.2	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71573 AN: 151496 Hom.: 17727 Cov.: 30

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.494

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.472 AC: 71571 AN: 151614 Hom.: 17724 Cov.: 30 AF XY: 0.474 AC XY: 35120 AN XY: 74032

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.490

Alfa AF: 0.520 Hom.: 19607

Bravo AF: 0.455

Asia WGS AF: 0.418 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	10
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3087404; hg19: chr12-54581614;