12-54182016-C-A

Variant names:

• chr12-54182016-C-A
• rs2233921
• NM_001243787.2:c.*80G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243787.2(SMUG1):​c.*80G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,510,624 control chromosomes in the GnomAD database, including 158,229 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 0.36 (12093 hom., cov: 31)
  • Exomes 𝑓: 0.46 (146136 hom.)
• Consequence: SMUG1 NM_001243787.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 41 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMUG1	NM_001243787.2	c.*80G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000682136.1	NP_001230716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMUG1	ENST00000682136.1	c.*80G>T		3_prime_UTR_variant	Exon 4 of 4		NM_001243787.2	ENSP00000507590.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54912 AN: 151788 Hom.: 12101 Cov.: 31

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.459 AC: 623011 AN: 1358718 Hom.: 146136 Cov.: 41 AF XY: 0.458 AC XY: 304443 AN XY: 664578

African (AFR) AF: 0.0832 AC: 2501 AN: 30074

American (AMR) AF: 0.383 AC: 10899 AN: 28458

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 8379 AN: 19832

East Asian (EAS) AF: 0.403 AC: 15591 AN: 38686

South Asian (SAS) AF: 0.400 AC: 27549 AN: 68842

European-Finnish (FIN) AF: 0.545 AC: 27097 AN: 49760

Middle Eastern (MID) AF: 0.439 AC: 1694 AN: 3856

European-Non Finnish (NFE) AF: 0.475 AC: 504663 AN: 1063432

Other (OTH) AF: 0.442 AC: 24638 AN: 55778

GnomAD4 genome AF: 0.361 AC: 54884 AN: 151906 Hom.: 12093 Cov.: 31 AF XY: 0.368 AC XY: 27327 AN XY: 74232

African (AFR) AF: 0.0988 AC: 4095 AN: 41454

American (AMR) AF: 0.406 AC: 6191 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1446 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2024 AN: 5144

South Asian (SAS) AF: 0.395 AC: 1898 AN: 4806

European-Finnish (FIN) AF: 0.557 AC: 5854 AN: 10512

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.472 AC: 32044 AN: 67958

Other (OTH) AF: 0.393 AC: 828 AN: 2106

Alfa AF: 0.415 Hom.: 11795

Bravo AF: 0.338

Asia WGS AF: 0.362 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.52
PhyloP100		0.30
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: rs2233921; hg19: chr12-54575800; COSMIC: COSV54540527; COSMIC: COSV54540527;