dbSNP rs185963873: SMG7:p.Met19Ile (chr1-183512864-G-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_001394140.1(SMG7):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMG7
NM_001394140.1 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.10

Publications

2 publications found

Variant links:

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

SMG7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 25 codons. Genomic position: 183515939. Lost 0.022 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394140.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMG7	NM_001375584.1	MANE Select	c.57G>A	p.Met19Ile	missense	Exon 2 of 23	NP_001362513.1	A0A8I5KYV3
SMG7	NM_001394140.1		c.3G>A	p.Met1?	start_lost	Exon 3 of 23	NP_001381069.1
SMG7	NM_001394145.1		c.3G>A	p.Met1?	start_lost	Exon 5 of 25	NP_001381074.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMG7	ENST00000688051.1	MANE Select	c.57G>A	p.Met19Ile	missense	Exon 2 of 23	ENSP00000510175.1	A0A8I5KYV3
SMG7	ENST00000507469.5	TSL:1	c.57G>A	p.Met19Ile	missense	Exon 2 of 23	ENSP00000425133.1	Q92540-4
SMG7	ENST00000347615.6	TSL:1	c.57G>A	p.Met19Ile	missense	Exon 2 of 22	ENSP00000340766.2	Q92540-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1312686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656056

African (AFR)

AF:

0.00

AC:

AN:

29860

American (AMR)

AF:

0.00

AC:

AN:

39978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24056

East Asian (EAS)

AF:

0.00

AC:

AN:

35828

South Asian (SAS)

AF:

0.00

AC:

AN:

77208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4580

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

995830

Other (OTH)

AF:

0.00

AC:

AN:

54146

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0062

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

9.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.33

REVEL

Benign

0.26

Sift

Uncertain

0.015

Sift4G

Benign

0.39

Polyphen

0.025

Vest4

0.63

MutPred

0.39

Loss of catalytic residue at M48 (P = 0.0094)

MVP

0.56

MPC

1.0

ClinPred

0.83

GERP RS

5.4

Varity_R

0.22

gMVP

0.69

Mutation Taster

=225/75

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over