11-95172947-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144665.4(SESN3):​c.*308C>G variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000095 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SESN3	NM_144665.4	c.*308C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000536441.7	NP_653266.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SESN3	ENST00000536441.7	c.*308C>G		3_prime_UTR_variant	Exon 10 of 10	2	NM_144665.4	ENSP00000441927.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000952 AC: 1 AN: 104990 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 53310

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3926

American (AMR) AF: 0.00 AC: 0 AN: 4390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4596

East Asian (EAS) AF: 0.00 AC: 0 AN: 8972

South Asian (SAS) AF: 0.00 AC: 0 AN: 2198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 570

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66652

Other (OTH) AF: 0.00 AC: 0 AN: 7178

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.3
DANN	Benign	0.69
PhyloP100		0.96

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;