Genetic Variant NM_133491.5:c.294G>A (chr17-7626953-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_133491.5(SAT2):c.294G>A(p.Pro98Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,612,372 control chromosomes in the GnomAD database, including 111,451 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 0.29 ( 7874 hom., cov: 31)

Exomes 𝑓: 0.37 ( 103577 hom. )

Consequence

SAT2
NM_133491.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.25

Publications

42 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=-6.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAT2	NM_133491.5 link	c.294G>A	p.Pro98Pro	synonymous_variant	Exon 4 of 6	ENST00000269298.10	NP_597998.1	Q96F10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAT2	ENST00000269298.10 link	c.294G>A	p.Pro98Pro	synonymous_variant	Exon 4 of 6	1	NM_133491.5	ENSP00000269298.5		Q96F10

Frequencies

GnomAD3 genomes

AF:

0.290

AC:

43985

AN:

151818

Hom.:

7873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.330

GnomAD2 exomes

AF:

0.352

AC:

88422

AN:

251072

AF XY:

0.371

show subpopulations

Gnomad AFR exome

AF:

0.0662

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.280

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.370

AC:

540658

AN:

1460436

Hom.:

103577

Cov.:

AF XY:

0.376

AC XY:

273352

AN XY:

726638

show subpopulations

African (AFR)

AF:

0.0622

AC:

2083

AN:

33472

American (AMR)

AF:

0.266

AC:

11910

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

11389

AN:

26126

East Asian (EAS)

AF:

0.266

AC:

10573

AN:

39694

South Asian (SAS)

AF:

0.477

AC:

41112

AN:

86220

European-Finnish (FIN)

AF:

0.365

AC:

19457

AN:

53340

Middle Eastern (MID)

AF:

0.504

AC:

2896

AN:

5750

European-Non Finnish (NFE)

AF:

0.377

AC:

419188

AN:

1110762

Other (OTH)

AF:

0.365

AC:

22050

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

17503

35006

52510

70013

87516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12910

25820

38730

51640

64550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.290

AC:

43987

AN:

151936

Hom.:

7874

Cov.:

AF XY:

0.294

AC XY:

21825

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.0761

AC:

3159

AN:

41498

American (AMR)

AF:

0.287

AC:

4371

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1514

AN:

3466

East Asian (EAS)

AF:

0.282

AC:

1448

AN:

5136

South Asian (SAS)

AF:

0.468

AC:

2249

AN:

4806

European-Finnish (FIN)

AF:

0.378

AC:

3992

AN:

10562

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.384

AC:

26061

AN:

67918

Other (OTH)

AF:

0.328

AC:

690

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1439

2878

4318

5757

7196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.350

Hom.:

30019

Bravo

AF:

0.268

Asia WGS

AF:

0.332

AC:

1154

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.0

(source)

DANN

Benign

0.79

PhyloP100

-6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over