11-95191585-G-C

Position:

• chr11-95191585-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144665.4(SESN3):​c.161C>G​(p.Thr54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SESN3 NM_144665.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14406773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SESN3	NM_144665.4	c.161C>G	p.Thr54Arg	missense_variant	3/10	ENST00000536441.7	NP_653266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SESN3	ENST00000536441.7	c.161C>G	p.Thr54Arg	missense_variant	3/10	2	NM_144665.4	ENSP00000441927	P1
LNCRNA-IUR	ENST00000657854.2	n.508+33782G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 25, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;T
Eigen	Benign	0.039
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.040
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.24	T;T;.
Polyphen		0.095	B;B;.
Vest4		0.085
MutPred		0.38		Loss of phosphorylation at T54 (P = 0.0493);Loss of phosphorylation at T54 (P = 0.0493);.;
MVP		0.10
MPC		0.93
ClinPred		0.42	T
GERP RS		5.5
Varity_R		0.054
gMVP		0.64

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: rs1320887348; hg19: chr11-94924749;