rs10494394

chr1-28281827-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_031459.5(SESN2):c.*1025A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0293 in 152,258 control chromosomes in the GnomAD database, including 102 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 0.029 (102 hom., cov: 32)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: SESN2 NM_031459.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

Genes affected

SESN2 (HGNC:20746): (sestrin 2) This gene encodes a member of the sestrin family of PA26-related proteins. The encoded protein may function in the regulation of cell growth and survival. This protein may be involved in cellular response to different stress conditions. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0293 (4454/152178) while in subpopulation NFE AF= 0.05 (3401/67976). AF 95% confidence interval is 0.0486. There are 102 homozygotes in gnomad4. There are 1936 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 102 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SESN2	NM_031459.5	c.*1025A>G		3_prime_UTR_variant	10/10	ENST00000253063.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SESN2	ENST00000253063.4	c.*1025A>G		3_prime_UTR_variant	10/10	1	NM_031459.5	P1

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4457 AN: 152060 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.00864

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00664

Gnomad FIN AF: 0.0218

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.0125 AC: 1 AN: 80 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0152

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0293 AC: 4454 AN: 152178 Hom.: 102 Cov.: 32 AF XY: 0.0260 AC XY: 1936 AN XY: 74414

Gnomad4 AFR AF: 0.00862

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00644

Gnomad4 FIN AF: 0.0218

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0432 Hom.: 160

Bravo AF: 0.0282

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.4
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10494394; hg19: chr1-28608338;