Variant 11-95191611-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_144665.4(SESN3):c.145-10T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,578,724 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

SESN3
NM_144665.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.02354

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.789

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 11-95191611-A-C is Benign according to our data. Variant chr11-95191611-A-C is described in ClinVar as [Benign]. Clinvar id is 787096.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1573/136412) while in subpopulation AFR AF= 0.042 (1494/35588). AF 95% confidence interval is 0.0402. There are 34 homozygotes in gnomad4. There are 733 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SESN3	NM_144665.4 linkuse as main transcript	c.145-10T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000536441.7	NP_653266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SESN3	ENST00000536441.7 linkuse as main transcript	c.145-10T>G		splice_polypyrimidine_tract_variant, intron_variant		2	NM_144665.4	ENSP00000441927	P1	P58005-1
LNCRNA-IUR	ENST00000657854.2 linkuse as main transcript	n.508+33808A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1575

AN:

136328

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00410

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000154

Gnomad OTH

AF:

0.00681

GnomAD3 exomes

AF:

0.00310

AC:

654

AN:

211118

Hom.:

AF XY:

0.00216

AC XY:

247

AN XY:

114242

show subpopulations

Gnomad AFR exome

AF:

0.0425

Gnomad AMR exome

AF:

0.00161

Gnomad ASJ exome

AF:

0.000217

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00242

GnomAD4 exome

AF:

0.00108

AC:

1556

AN:

1442312

Hom.:

Cov.:

AF XY:

0.000931

AC XY:

668

AN XY:

717634

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.00187

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000884

Gnomad4 OTH exome

AF:

0.00258

GnomAD4 genome

AF:

0.0115

AC:

1573

AN:

136412

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

733

AN XY:

66214

show subpopulations

Gnomad4 AFR

AF:

0.0420

Gnomad4 AMR

AF:

0.00410

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000154

Gnomad4 OTH

AF:

0.00681

Alfa

AF:

0.00699

Hom.:

Bravo

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.024

dbscSNV1_RF

Benign

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over