rs216182

Positions:

• chr17-2269769-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SMG6	NM_017575.5	c.2661+12878T>C		intron_variant		ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.2661+12878T>C		intron_variant		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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.237

Alfa AF: 0.266 Hom.: 7454

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

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: rs216182; hg19: chr17-2173063;