17-2065630-CC-AG

Variant names:

• chr17-2065630-CC-AG
• NM_017575.5:c.3884_3885delGGinsCT
• SMG6 p.Arg1295Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017575.5(SMG6):​c.3884_3885delGGinsCT​(p.Arg1295Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1295Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMG6 NM_017575.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.94
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017575.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	NM_017575.5	MANE Select	c.3884_3885delGGinsCT	p.Arg1295Pro	missense	N/A	NP_060045.4
	SMG6	NM_001256827.2		c.1160_1161delGGinsCT	p.Arg387Pro	missense	N/A	NP_001243756.1	Q86US8-3
	SMG6	NM_001256828.1		c.1160_1161delGGinsCT	p.Arg387Pro	missense	N/A	NP_001243757.1	Q86US8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG6	ENST00000263073.11	TSL:1 MANE Select	c.3884_3885delGGinsCT	p.Arg1295Pro	missense	N/A	ENSP00000263073.5	Q86US8-1
	SMG6	ENST00000354901.8	TSL:1	c.1160_1161delGGinsCT	p.Arg387Pro	missense	N/A	ENSP00000346977.4	Q86US8-3
	SMG6	ENST00000573166.5	TSL:1	n.2214_2215delGGinsCT		non_coding_transcript_exon	Exon 5 of 7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-1968924;