1-183517758-C-G

Variant names:

• chr1-183517758-C-G
• rs1391258803
• NM_001375584.1:c.250C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001375584.1(SMG7):​c.250C>G​(p.Arg84Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R84W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMG7 NM_001375584.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.250C>G	p.Arg84Gly	missense	Exon 4 of 23	NP_001362513.1	A0A8I5KYV3
	SMG7	NM_001350220.2		c.337C>G	p.Arg113Gly	missense	Exon 6 of 25	NP_001337149.1	A0A8I5KSL3
	SMG7	NM_001394133.1		c.337C>G	p.Arg113Gly	missense	Exon 5 of 24	NP_001381062.1	A0A8I5KSL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMG7	ENST00000688051.1	MANE Select	c.250C>G	p.Arg84Gly	missense	Exon 4 of 23	ENSP00000510175.1	A0A8I5KYV3
	SMG7	ENST00000507469.5	TSL:1	c.250C>G	p.Arg84Gly	missense	Exon 4 of 23	ENSP00000425133.1	Q92540-4
	SMG7	ENST00000347615.6	TSL:1	c.250C>G	p.Arg84Gly	missense	Exon 4 of 22	ENSP00000340766.2	Q92540-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.58		Loss of loop (P = 0.0512)
MVP		0.65
MPC		2.1
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.67
Mutation Taster		=13/87	disease causing

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: rs1391258803; hg19: chr1-183486893;