Genetic Variant SMG7:c.*1686G>T (chr1-183553617-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001375584.1(SMG7):c.*1686G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.00060 ( 6 hom., cov: 25)

Exomes 𝑓: 0.00042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SMG7
NM_001375584.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

15 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMG7	NM_001375584.1	MANE Select	c.*1686G>T	3_prime_UTR	Exon 23 of 23	NP_001362513.1	A0A8I5KYV3
SMG7	NM_001350220.2		c.*1686G>T	3_prime_UTR	Exon 25 of 25	NP_001337149.1	A0A8I5KSL3
SMG7	NM_001394133.1		c.*1686G>T	3_prime_UTR	Exon 24 of 24	NP_001381062.1	A0A8I5KSL3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SMG7	ENST00000688051.1	MANE Select	c.*1686G>T	3_prime_UTR	Exon 23 of 23	ENSP00000510175.1	A0A8I5KYV3
SMG7	ENST00000507469.5	TSL:1	c.*416G>T	3_prime_UTR	Exon 23 of 23	ENSP00000425133.1	Q92540-4
SMG7	ENST00000347615.6	TSL:1	c.*1686G>T	3_prime_UTR	Exon 22 of 22	ENSP00000340766.2	Q92540-1

Frequencies

GnomAD3 genomes

AF:

0.000596

AC:

AN:

120806

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000816

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000934

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000139

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00122

Gnomad OTH

AF:

0.000627

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000424

AC:

AN:

9424

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

4946

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

238

American (AMR)

AF:

0.00107

AC:

AN:

936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

218

East Asian (EAS)

AF:

0.00

AC:

AN:

256

South Asian (SAS)

AF:

0.00

AC:

AN:

1168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000516

AC:

AN:

5810

Other (OTH)

AF:

0.00

AC:

AN:

444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000596

AC:

AN:

120880

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

AN XY:

57684

show subpopulations

African (AFR)

AF:

0.0000814

AC:

AN:

36844

American (AMR)

AF:

0.0000934

AC:

AN:

10710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2860

East Asian (EAS)

AF:

0.00

AC:

AN:

3480

South Asian (SAS)

AF:

0.00

AC:

AN:

3266

European-Finnish (FIN)

AF:

0.000139

AC:

AN:

7178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.00122

AC:

AN:

54040

Other (OTH)

AF:

0.000621

AC:

AN:

1610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000841

Hom.:

304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.19

(source)

DANN

Benign

0.076

PhyloP100

-1.7

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over