rs4790881

Positions:

• chr17-2165638-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
SMG6	NM_017575.5	c.3357+7020G>T		intron_variant		ENST00000263073.11	NP_060045.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG6	ENST00000263073.11	c.3357+7020G>T		intron_variant		1	NM_017575.5	ENSP00000263073	P1

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

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.752

Alfa AF: 0.706 Hom.: 34436

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

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: rs4790881; hg19: chr17-2068932; COSMIC: COSV53974737;