rs17761864

Variant names:

• chr17-2268343-C-A
• rs17761864
• NM_017575.5:c.2661+14304G>T

Your query was ambiguous. Multiple possible variants found:

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

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+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
• Publications: 34 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017575.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	NM_017575.5	MANE Select	c.2661+14304G>T		intron	N/A	NP_060045.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	ENST00000263073.11	TSL:1 MANE Select	c.2661+14304G>T		intron	N/A	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

African (AFR) AF: 0.138 AC: 5726 AN: 41524

American (AMR) AF: 0.362 AC: 5526 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3466

East Asian (EAS) AF: 0.111 AC: 576 AN: 5178

South Asian (SAS) AF: 0.169 AC: 813 AN: 4822

European-Finnish (FIN) AF: 0.371 AC: 3901 AN: 10528

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23642 AN: 67964

Other (OTH) AF: 0.304 AC: 641 AN: 2110

Alfa AF: 0.311 Hom.: 14897

Bravo AF: 0.278

Asia WGS AF: 0.131 AC: 458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.31
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: rs17761864; hg19: chr17-2171637;