rs11078884

Variant names:

• chr17-2241899-T-C
• rs11078884
• NM_017575.5:c.2723+2759A>G

Variant summary

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

The NM_017575.5(SMG6):​c.2723+2759A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,264 control chromosomes in the GnomAD database, including 1,166 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 0.10 (1166 hom., cov: 33)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 10 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	NM_017575.5	MANE Select	c.2723+2759A>G		intron	N/A	NP_060045.4
	SMG6	NM_001256827.2		c.-2+2759A>G		intron	N/A	NP_001243756.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	ENST00000263073.11	TSL:1 MANE Select	c.2723+2759A>G		intron	N/A	ENSP00000263073.5
	SMG6	ENST00000354901.8	TSL:1	c.-2+2759A>G		intron	N/A	ENSP00000346977.4
	SMG6	ENST00000883972.1		c.2723+2759A>G		intron	N/A	ENSP00000554031.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15905 AN: 152146 Hom.: 1165 Cov.: 33

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.104 AC: 15907 AN: 152264 Hom.: 1166 Cov.: 33 AF XY: 0.101 AC XY: 7547 AN XY: 74446

African (AFR) AF: 0.0273 AC: 1133 AN: 41576

American (AMR) AF: 0.120 AC: 1828 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0422 AC: 204 AN: 4832

European-Finnish (FIN) AF: 0.0907 AC: 961 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10773 AN: 68010

Other (OTH) AF: 0.133 AC: 280 AN: 2108

Alfa AF: 0.104 Hom.: 644

Bravo AF: 0.104

Asia WGS AF: 0.0200 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.69
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs11078884; hg19: chr17-2145193; COSMIC: COSV53975009; COSMIC: COSV53975009;