NM_001375584.1:c.710_711delGAinsAG

Variant names:

• chr1-183529400-GA-AG
• NM_001375584.1:c.710_711delGAinsAG
• SMG7 p.Arg237Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001375584.1(SMG7):​c.710_711delGAinsAG​(p.Arg237Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. R237R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMG7 NM_001375584.1 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.12
• Publications: 0 publications found

Genes affected

SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

SMG7 Gene-Disease associations (from GenCC):

• autoimmune disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375584.1. 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
	SMG7	NM_001375584.1	MANE Select	c.710_711delGAinsAG	p.Arg237Gln	missense splice_region	N/A	NP_001362513.1	A0A8I5KYV3
	SMG7	NM_001350220.2		c.797_798delGAinsAG	p.Arg266Gln	missense splice_region	N/A	NP_001337149.1	A0A8I5KSL3
	SMG7	NM_001394133.1		c.797_798delGAinsAG	p.Arg266Gln	missense splice_region	N/A	NP_001381062.1	A0A8I5KSL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG7	ENST00000688051.1	MANE Select	c.710_711delGAinsAG	p.Arg237Gln	missense splice_region	N/A	ENSP00000510175.1	A0A8I5KYV3
	SMG7	ENST00000507469.5	TSL:1	c.710_711delGAinsAG	p.Arg237Gln	missense splice_region	N/A	ENSP00000425133.1	Q92540-4
	SMG7	ENST00000347615.6	TSL:1	c.710_711delGAinsAG	p.Arg237Gln	missense splice_region	N/A	ENSP00000340766.2	Q92540-1

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		9.1

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: chr1-183498535;