Genetic Variant SESN3:c.*308C>T (chr11-95172947-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_144665.4(SESN3):c.*308C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 256,084 control chromosomes in the GnomAD database, including 25,464 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 0.42 ( 14394 hom., cov: 30)

Exomes 𝑓: 0.45 ( 11070 hom. )

Consequence

SESN3
NM_144665.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.958

Publications

18 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]

SESN3 links:

LNCRNA-IUR (HGNC:55755): (lncRNA imatinib upregulated)

LNCRNA-IUR links:

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=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SESN3	NM_144665.4 link	c.*308C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000536441.7	NP_653266.2	P58005-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SESN3	ENST00000536441.7 link	c.*308C>T		3_prime_UTR_variant	Exon 10 of 10	2	NM_144665.4	ENSP00000441927.1		P58005-1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64185

AN:

151474

Hom.:

14407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.438

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.447

AC:

46706

AN:

104498

Hom.:

11070

Cov.:

AF XY:

0.447

AC XY:

23699

AN XY:

53044

show subpopulations

African (AFR)

AF:

0.331

AC:

1289

AN:

3892

American (AMR)

AF:

0.456

AC:

1992

AN:

4368

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1795

AN:

4570

East Asian (EAS)

AF:

0.669

AC:

5978

AN:

8936

South Asian (SAS)

AF:

0.559

AC:

1225

AN:

2190

European-Finnish (FIN)

AF:

0.360

AC:

2340

AN:

6492

Middle Eastern (MID)

AF:

0.486

AC:

274

AN:

564

European-Non Finnish (NFE)

AF:

0.432

AC:

28630

AN:

66348

Other (OTH)

AF:

0.446

AC:

3183

AN:

7138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1204

2408

3611

4815

6019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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

AF:

0.424

AC:

64198

AN:

151586

Hom.:

14394

Cov.:

AF XY:

0.426

AC XY:

31542

AN XY:

74046

show subpopulations

African (AFR)

AF:

0.341

AC:

14086

AN:

41310

American (AMR)

AF:

0.459

AC:

6997

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

1310

AN:

3466

East Asian (EAS)

AF:

0.748

AC:

3857

AN:

5156

South Asian (SAS)

AF:

0.591

AC:

2839

AN:

4802

European-Finnish (FIN)

AF:

0.356

AC:

3724

AN:

10474

Middle Eastern (MID)

AF:

0.507

AC:

148

AN:

292

European-Non Finnish (NFE)

AF:

0.438

AC:

29683

AN:

67844

Other (OTH)

AF:

0.439

AC:

925

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1795

3590

5385

7180

8975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<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:

0.441

Hom.:

29488

Bravo

AF:

0.429

Asia WGS

AF:

0.589

AC:

2047

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.0

(source)

DANN

Benign

0.75

PhyloP100

0.96

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over