rs684856

Positions:

• chr11-95172947-G-A
• chr11-95172947-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958

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)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SESN3	NM_144665.4	c.*308C>T		3_prime_UTR_variant	10/10	ENST00000536441.7	NP_653266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SESN3	ENST00000536441.7	c.*308C>T		3_prime_UTR_variant	10/10	2	NM_144665.4	ENSP00000441927	P1
LNCRNA-IUR	ENST00000657854.2	n.508+15144G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64185 AN: 151474 Hom.: 14407 Cov.: 30

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.: 0 AF XY: 0.447 AC XY: 23699 AN XY: 53044

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.424 AC: 64198 AN: 151586 Hom.: 14394 Cov.: 30 AF XY: 0.426 AC XY: 31542 AN XY: 74046

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.439

Alfa AF: 0.442 Hom.: 21564

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
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs684856; hg19: chr11-94906111;