rs684856

Variant names:

• chr11-95172947-G-A
• rs684856
• NM_144665.4:c.*308C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144665.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SESN3	NM_144665.4	MANE Select	c.*308C>T		3_prime_UTR	Exon 10 of 10	NP_653266.2
	SESN3	NM_001271594.2		c.*308C>T		3_prime_UTR	Exon 9 of 9	NP_001258523.1	P58005-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SESN3	ENST00000536441.7	TSL:2 MANE Select	c.*308C>T		3_prime_UTR	Exon 10 of 10	ENSP00000441927.1	P58005-1
	LNCRNA-IUR	ENST00000534864.7	TSL:4	n.626+15144G>A		intron	N/A
	LNCRNA-IUR	ENST00000534891.7	TSL:2	n.502+15144G>A		intron	N/A

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

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

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.0
DANN	Benign	0.75
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs684856; hg19: chr11-94906111;