Variant rs858521 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_133491.5(SAT2):c.305-36C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,611,592 control chromosomes in the GnomAD database, including 111,960 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.30 ( 8004 hom., cov: 30)

Exomes 𝑓: 0.37 ( 103956 hom. )

Consequence

SAT2
NM_133491.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

SAT2 (HGNC:23160): (spermidine/spermine N1-acetyltransferase family member 2) Enables diamine N-acetyltransferase activity and identical protein binding activity. Involved in polyamine metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SAT2 links:

SHBG (HGNC:10839): (sex hormone binding globulin) This gene encodes a steroid binding protein that was first described as a plasma protein secreted by the liver but is now thought to participate in the regulation of steroid responses. The encoded protein transports androgens and estrogens in the blood, binding each steroid molecule as a dimer formed from identical or nearly identical monomers. Polymorphisms in this gene have been associated with polycystic ovary syndrome and type 2 diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

SHBG links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAT2	NM_133491.5 linkuse as main transcript	c.305-36C>G		intron_variant		ENST00000269298.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAT2	ENST00000269298.10 linkuse as main transcript	c.305-36C>G		intron_variant		1	NM_133491.5	P1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45283

AN:

151702

Hom.:

8002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.376

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.477

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.340

GnomAD3 exomes

AF:

0.355

AC:

89306

AN:

251348

Hom.:

17136

AF XY:

0.373

AC XY:

50715

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0961

Gnomad AMR exome

AF:

0.258

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.280

Gnomad SAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.391

GnomAD4 exome

AF:

0.372

AC:

542376

AN:

1459772

Hom.:

103956

Cov.:

AF XY:

0.378

AC XY:

274274

AN XY:

726294

show subpopulations

Gnomad4 AFR exome

AF:

0.0923

Gnomad4 AMR exome

AF:

0.268

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.485

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.368

GnomAD4 genome

AF:

0.298

AC:

45288

AN:

151820

Hom.:

8004

Cov.:

AF XY:

0.303

AC XY:

22442

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.437

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.478

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.346

Hom.:

1724

Bravo

AF:

0.278

Asia WGS

AF:

0.338

AC:

1176

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.9

DANN

Benign

0.67

BranchPoint Hunter

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over