rs629508

Variant names:

• chr11-95189235-T-C
• rs629508
• NM_144665.4:c.525+544A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 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.525+544A>G		intron	N/A	NP_653266.2
	SESN3	NM_001271594.2		c.108+2169A>G		intron	N/A	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.525+544A>G		intron	N/A	ENSP00000441927.1	P58005-1
	SESN3	ENST00000416495.6	TSL:1	c.525+544A>G		intron	N/A	ENSP00000407008.2	P58005-3
	SESN3	ENST00000278499.6	TSL:2	c.108+2169A>G		intron	N/A	ENSP00000278499.2	P58005-4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44855 AN: 151624 Hom.: 7633 Cov.: 32

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

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

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs629508;

hg19: chr11-94922399;