rs11078884

Positions:

• chr17-2241899-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMG6	NM_017575.5	c.2723+2759A>G		intron_variant		ENST00000263073.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMG6	ENST00000263073.11	c.2723+2759A>G		intron_variant		1	NM_017575.5	P1
SMG6	ENST00000354901.8	c.-2+2759A>G		intron_variant		1
SMG6	ENST00000570606.5	c.-1-5262A>G		intron_variant		4
SMG6	ENST00000570659.5	c.-2+2759A>G		intron_variant		4

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

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.0907

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.133

Alfa AF: 0.135 Hom.: 250

Bravo AF: 0.104

Asia WGS AF: 0.0200 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs11078884; hg19: chr17-2145193; COSMIC: COSV53975009; COSMIC: COSV53975009;