rs216182

Variant names:

• chr17-2269769-A-G
• rs216182
• NM_017575.5:c.2661+12878T>C

Variant summary

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

The NM_017575.5(SMG6):​c.2661+12878T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,116 control chromosomes in the GnomAD database, including 5,329 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 0.25 (5329 hom., cov: 32)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 11 publications found

Genes affected

SMG6 (HGNC:17809): (SMG6 nonsense mediated mRNA decay factor) This gene encodes a component of the telomerase ribonucleoprotein complex responsible for the replication and maintenance of chromosome ends. The encoded protein also plays a role in the nonsense-mediated mRNA decay (NMD) pathway, providing the endonuclease activity near the premature translation termination codon that is needed to initiate NMD. Alternatively spliced transcript variants encoding distinct protein isoforms have been described. [provided by RefSeq, Feb 2014]

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 (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG6	NM_017575.5	c.2661+12878T>C		intron_variant	Intron 8 of 18	ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.2661+12878T>C		intron_variant	Intron 8 of 18	1	NM_017575.5	ENSP00000263073.5

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37392 AN: 151998 Hom.: 5332 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.246 AC: 37396 AN: 152116 Hom.: 5329 Cov.: 32 AF XY: 0.252 AC XY: 18756 AN XY: 74338

African (AFR) AF: 0.142 AC: 5908 AN: 41544

American (AMR) AF: 0.219 AC: 3346 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3464

East Asian (EAS) AF: 0.583 AC: 3013 AN: 5166

South Asian (SAS) AF: 0.396 AC: 1913 AN: 4826

European-Finnish (FIN) AF: 0.289 AC: 3050 AN: 10544

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18505 AN: 67988

Other (OTH) AF: 0.237 AC: 499 AN: 2108

Alfa AF: 0.259 Hom.: 9092

Bravo AF: 0.231

Asia WGS AF: 0.424 AC: 1474 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	0.32
DANN	Benign	0.51
PhyloP100		-1.2
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: rs216182; hg19: chr17-2173063;