17-2223210-G-C

Position:

• chr17-2223210-G-C

Variant summary

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

The ENST00000263073.11(SMG6):​c.2869+13282C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,094 control chromosomes in the GnomAD database, including 9,696 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 0.35 (9696 hom., cov: 32)
• Consequence: SMG6 ENST00000263073.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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=-0.53).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG6	NM_017575.5	c.2869+13282C>G		intron_variant		ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.2869+13282C>G		intron_variant		1	NM_017575.5	ENSP00000263073	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53782 AN: 151976 Hom.: 9691 Cov.: 32

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.354 AC: 53825 AN: 152094 Hom.: 9696 Cov.: 32 AF XY: 0.354 AC XY: 26348 AN XY: 74362

Gnomad4 AFR AF: 0.368

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.364

Alfa AF: 0.326 Hom.: 4454

Bravo AF: 0.356

Asia WGS AF: 0.329 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.75

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: rs216172; hg19: chr17-2126504; COSMIC: COSV53974948;