Variant rs13894 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.376C>T(p.Arg126Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 1,613,918 control chromosomes in the GnomAD database, including 4,557 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.071 ( 387 hom., cov: 31)

Exomes 𝑓: 0.074 ( 4170 hom. )

Consequence

SAT2
NM_133491.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026856065).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0996 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.376C>T	p.Arg126Cys	missense_variant	6/6	ENST00000269298.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAT2	ENST00000269298.10 linkuse as main transcript	c.376C>T	p.Arg126Cys	missense_variant	6/6	1	NM_133491.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0713

AC:

10856

AN:

152158

Hom.:

384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0552

Gnomad ASJ

AF:

0.0893

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0554

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0736

Gnomad OTH

AF:

0.0666

GnomAD3 exomes

AF:

0.0695

AC:

17433

AN:

250946

Hom.:

694

AF XY:

0.0717

AC XY:

9725

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.0759

Gnomad AMR exome

AF:

0.0394

Gnomad ASJ exome

AF:

0.0896

Gnomad EAS exome

AF:

0.0445

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.0548

Gnomad NFE exome

AF:

0.0723

Gnomad OTH exome

AF:

0.0677

GnomAD4 exome

AF:

0.0736

AC:

107596

AN:

1461642

Hom.:

4170

Cov.:

AF XY:

0.0749

AC XY:

54427

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0807

Gnomad4 AMR exome

AF:

0.0399

Gnomad4 ASJ exome

AF:

0.0896

Gnomad4 EAS exome

AF:

0.0540

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0534

Gnomad4 NFE exome

AF:

0.0733

Gnomad4 OTH exome

AF:

0.0762

GnomAD4 genome

AF:

0.0713

AC:

10863

AN:

152276

Hom.:

387

Cov.:

AF XY:

0.0702

AC XY:

5224

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0761

Gnomad4 AMR

AF:

0.0552

Gnomad4 ASJ

AF:

0.0893

Gnomad4 EAS

AF:

0.0434

Gnomad4 SAS

AF:

0.107

Gnomad4 FIN

AF:

0.0554

Gnomad4 NFE

AF:

0.0736

Gnomad4 OTH

AF:

0.0692

Alfa

AF:

0.0714

Hom.:

794

Bravo

AF:

0.0690

TwinsUK

AF:

0.0766

AC:

284

ALSPAC

AF:

0.0708

AC:

273

ESP6500AA

AF:

0.0733

AC:

323

ESP6500EA

AF:

0.0721

AC:

620

ExAC

AF:

0.0725

AC:

8802

Asia WGS

AF:

0.100

AC:

347

AN:

3478

EpiCase

AF:

0.0646

EpiControl

AF:

0.0650

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.082

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.93

D;D

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.00059

P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.2

D;.

REVEL

Benign

0.21

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.033

D;D

Polyphen

1.0

D;.

Vest4

0.39

MPC

1.3

ClinPred

0.024

GERP RS

4.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.57

gMVP

0.60

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

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