rs17761864

Positions:

• chr17-2268343-C-A
• chr17-2268343-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017575.5(SMG6):​c.2661+14304G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,080 control chromosomes in the GnomAD database, including 6,954 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 0.28 (6954 hom., cov: 32)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG6	NM_017575.5	c.2661+14304G>T		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+14304G>T		intron_variant		1	NM_017575.5	ENSP00000263073.5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42617 AN: 151962 Hom.: 6949 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.280 AC: 42634 AN: 152080 Hom.: 6954 Cov.: 32 AF XY: 0.280 AC XY: 20777 AN XY: 74314

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.304

Alfa AF: 0.289 Hom.: 1776

Bravo AF: 0.278

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.73

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: rs17761864; hg19: chr17-2171637;