rs3760229

Variant names:

• chr17-2302820-G-A
• rs3760229
• NM_017575.5:c.88+813C>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.88+813C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 152,082 control chromosomes in the GnomAD database, including 1,299 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 0.093 (1299 hom., cov: 32)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG6	NM_017575.5	c.88+813C>T		intron_variant	Intron 1 of 18	ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.88+813C>T		intron_variant	Intron 1 of 18	1	NM_017575.5	ENSP00000263073.5

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14106 AN: 151964 Hom.: 1298 Cov.: 32

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0967

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0927 AC: 14105 AN: 152082 Hom.: 1299 Cov.: 32 AF XY: 0.0968 AC XY: 7199 AN XY: 74366

African (AFR) AF: 0.0285 AC: 1184 AN: 41488

American (AMR) AF: 0.0850 AC: 1299 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2733 AN: 5164

South Asian (SAS) AF: 0.117 AC: 562 AN: 4808

European-Finnish (FIN) AF: 0.114 AC: 1210 AN: 10580

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0967 AC: 6574 AN: 67978

Other (OTH) AF: 0.0829 AC: 175 AN: 2110

Alfa AF: 0.0891 Hom.: 867

Bravo AF: 0.0876

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3760229; hg19: chr17-2206114;