NM_144665.4:c.525+544A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_144665.4(SESN3):​c.525+544A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,742 control chromosomes in the GnomAD database, including 7,636 homozygotes. 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 0.30 ( 7636 hom., cov: 32)

Consequence

SESN3
NM_144665.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.533

Publications

3 publications found
Variant links:
Genes affected
SESN3 (HGNC:23060): (sestrin 3) This gene encodes a member of the sestrin family of stress-induced proteins. The encoded protein reduces the levels of intracellular reactive oxygen species induced by activated Ras downstream of RAC-alpha serine/threonine-protein kinase (Akt) and FoxO transcription factor. The protein is required for normal regulation of blood glucose, insulin resistance and plays a role in lipid storage in obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]
LNCRNA-IUR (HGNC:55755): (lncRNA imatinib upregulated)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SESN3NM_144665.4 linkc.525+544A>G intron_variant Intron 4 of 9 ENST00000536441.7 NP_653266.2 P58005-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SESN3ENST00000536441.7 linkc.525+544A>G intron_variant Intron 4 of 9 2 NM_144665.4 ENSP00000441927.1 P58005-1

Frequencies

GnomAD3 genomes
AF:
0.296
AC:
44855
AN:
151624
Hom.:
7633
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.127
Gnomad AMI
AF:
0.670
Gnomad AMR
AF:
0.341
Gnomad ASJ
AF:
0.319
Gnomad EAS
AF:
0.277
Gnomad SAS
AF:
0.296
Gnomad FIN
AF:
0.433
Gnomad MID
AF:
0.342
Gnomad NFE
AF:
0.362
Gnomad OTH
AF:
0.316
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.296
AC:
44861
AN:
151742
Hom.:
7636
Cov.:
32
AF XY:
0.299
AC XY:
22170
AN XY:
74156
show subpopulations
African (AFR)
AF:
0.127
AC:
5279
AN:
41464
American (AMR)
AF:
0.341
AC:
5178
AN:
15202
Ashkenazi Jewish (ASJ)
AF:
0.319
AC:
1107
AN:
3468
East Asian (EAS)
AF:
0.277
AC:
1432
AN:
5164
South Asian (SAS)
AF:
0.297
AC:
1432
AN:
4816
European-Finnish (FIN)
AF:
0.433
AC:
4569
AN:
10556
Middle Eastern (MID)
AF:
0.337
AC:
99
AN:
294
European-Non Finnish (NFE)
AF:
0.361
AC:
24495
AN:
67762
Other (OTH)
AF:
0.313
AC:
659
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1524
3048
4571
6095
7619
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
460
920
1380
1840
2300
<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:
0.347
Hom.:
16249
Bravo
AF:
0.284
Asia WGS
AF:
0.257
AC:
898
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
2.3
DANN
Benign
0.54
PhyloP100
-0.53
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs629508; hg19: chr11-94922399; API