Genetic Variant NM_001375584.1:c.401C>A (chr1-183526684-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001375584.1(SMG7):c.401C>A(p.Thr134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. T134M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SMG7
NM_001375584.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51

Publications

0 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13552153).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
SMG7	NM_001375584.1	MANE Select	c.401C>A	p.Thr134Lys	missense	Exon 5 of 23	NP_001362513.1	A0A8I5KYV3
SMG7	NM_001350220.2		c.488C>A	p.Thr163Lys	missense	Exon 7 of 25	NP_001337149.1	A0A8I5KSL3
SMG7	NM_001394133.1		c.488C>A	p.Thr163Lys	missense	Exon 6 of 24	NP_001381062.1	A0A8I5KSL3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SMG7	ENST00000688051.1	MANE Select	c.401C>A	p.Thr134Lys	missense	Exon 5 of 23	ENSP00000510175.1	A0A8I5KYV3
SMG7	ENST00000507469.5	TSL:1	c.401C>A	p.Thr134Lys	missense	Exon 5 of 23	ENSP00000425133.1	Q92540-4
SMG7	ENST00000347615.6	TSL:1	c.401C>A	p.Thr134Lys	missense	Exon 5 of 22	ENSP00000340766.2	Q92540-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461288

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111630

Other (OTH)

AF:

0.0000166

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0097

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0053

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

2.5

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.62

REVEL

Benign

0.11

Sift

Benign

0.079

Sift4G

Benign

0.16

Polyphen

0.52

Vest4

0.30

MutPred

0.46

Loss of helix (P = 0.0017)

MVP

0.32

MPC

1.3

ClinPred

0.58

GERP RS

4.7

Varity_R

0.091

gMVP

0.28

Mutation Taster

=52/48

polymorphism

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over