NM_017575.5:c.3357+7020G>T

Variant names:

• chr17-2165638-C-A
• rs4790881
• NM_017575.5:c.3357+7020G>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.3357+7020G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,154 control chromosomes in the GnomAD database, including 42,935 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 0.74 (42935 hom., cov: 33)
• Consequence: SMG6 NM_017575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 52 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMG6	NM_017575.5	c.3357+7020G>T		intron_variant	Intron 13 of 18	ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.3357+7020G>T		intron_variant	Intron 13 of 18	1	NM_017575.5	ENSP00000263073.5

Frequencies

GnomAD3 genomes AF: 0.743 AC: 113028 AN: 152036 Hom.: 42881 Cov.: 33

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.744 AC: 113143 AN: 152154 Hom.: 42935 Cov.: 33 AF XY: 0.738 AC XY: 54865 AN XY: 74390

African (AFR) AF: 0.876 AC: 36397 AN: 41540

American (AMR) AF: 0.768 AC: 11741 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2386 AN: 3470

East Asian (EAS) AF: 0.406 AC: 2100 AN: 5174

South Asian (SAS) AF: 0.606 AC: 2921 AN: 4824

European-Finnish (FIN) AF: 0.677 AC: 7160 AN: 10578

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47946 AN: 67966

Other (OTH) AF: 0.752 AC: 1584 AN: 2106

Alfa AF: 0.712 Hom.: 113860

Bravo AF: 0.760

Asia WGS AF: 0.573 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.30
PhyloP100		-0.30
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: rs4790881; hg19: chr17-2068932; COSMIC: COSV53974737;