17-2222311-G-A

Variant names:

• chr17-2222311-G-A
• rs1231206
• NM_017575.5:c.2869+14181C>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.2869+14181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,540 control chromosomes in the GnomAD database, including 10,261 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 0.36 (10261 hom., cov: 28)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• Publications: 48 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG6	NM_017575.5	c.2869+14181C>T		intron_variant	Intron 10 of 18	ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.2869+14181C>T		intron_variant	Intron 10 of 18	1	NM_017575.5	ENSP00000263073.5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55069 AN: 151422 Hom.: 10251 Cov.: 28

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.364 AC: 55119 AN: 151540 Hom.: 10261 Cov.: 28 AF XY: 0.364 AC XY: 26955 AN XY: 74036

African (AFR) AF: 0.403 AC: 16617 AN: 41258

American (AMR) AF: 0.354 AC: 5385 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1153 AN: 3464

East Asian (EAS) AF: 0.263 AC: 1357 AN: 5156

South Asian (SAS) AF: 0.378 AC: 1808 AN: 4782

European-Finnish (FIN) AF: 0.343 AC: 3607 AN: 10504

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23962 AN: 67852

Other (OTH) AF: 0.374 AC: 790 AN: 2110

Alfa AF: 0.351 Hom.: 28831

Bravo AF: 0.368

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.41
PhyloP100		-0.72
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: rs1231206; hg19: chr17-2125605; COSMIC: COSV53974927;