rs1994356

Variant names:

• chr12-54177381-T-C
• rs1994356
• ENST00000509864.5:n.396+5123A>G

Variant summary

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

The ENST00000509864.5(SMUG1):​n.396+5123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,130 control chromosomes in the GnomAD database, including 39,658 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 0.72 (39658 hom., cov: 32)
• Consequence: SMUG1 ENST00000509864.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.621
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMUG1	XR_007063064.1	n.1467+5123A>G		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMUG1	ENST00000509864.5	n.396+5123A>G		intron_variant	Intron 2 of 4	3		ENSP00000426440.1
SMUG1	ENST00000635234.1	n.116-5272A>G		intron_variant	Intron 2 of 4	5
SMUG1	ENST00000635546.1	n.406-2234A>G		intron_variant	Intron 4 of 8	5		ENSP00000489489.1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108992 AN: 152012 Hom.: 39642 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.714

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.717 AC: 109049 AN: 152130 Hom.: 39658 Cov.: 32 AF XY: 0.718 AC XY: 53406 AN XY: 74358

African (AFR) AF: 0.844 AC: 35029 AN: 41522

American (AMR) AF: 0.623 AC: 9517 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2374 AN: 3468

East Asian (EAS) AF: 0.633 AC: 3275 AN: 5172

South Asian (SAS) AF: 0.816 AC: 3936 AN: 4822

European-Finnish (FIN) AF: 0.708 AC: 7495 AN: 10586

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.665 AC: 45182 AN: 67970

Other (OTH) AF: 0.710 AC: 1499 AN: 2110

Alfa AF: 0.690 Hom.: 4748

Bravo AF: 0.711

Asia WGS AF: 0.725 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1994356; hg19: chr12-54571165;