rs858521

Variant names:

• chr17-7626829-G-C
• rs858521
• NM_133491.5:c.305-36C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-7626829-G-C
• chr17-7626829-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 30 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 rank	MANE	Protein	UniProt
SAT2	NM_133491.5	c.305-36C>G		intron_variant	Intron 4 of 5	ENST00000269298.10	NP_597998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAT2	ENST00000269298.10	c.305-36C>G		intron_variant	Intron 4 of 5	1	NM_133491.5	ENSP00000269298.5

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45283 AN: 151702 Hom.: 8002 Cov.: 30

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

GnomAD2 exomes AF: 0.355 AC: 89306 AN: 251348 AF XY: 0.373

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 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.: 33 AF XY: 0.378 AC XY: 274274 AN XY: 726294

African (AFR) AF: 0.0923 AC: 3085 AN: 33436

American (AMR) AF: 0.268 AC: 11966 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 11387 AN: 26120

East Asian (EAS) AF: 0.266 AC: 10570 AN: 39692

South Asian (SAS) AF: 0.485 AC: 41813 AN: 86228

European-Finnish (FIN) AF: 0.365 AC: 19484 AN: 53348

Middle Eastern (MID) AF: 0.507 AC: 2926 AN: 5766

European-Non Finnish (NFE) AF: 0.377 AC: 418924 AN: 1110122

Other (OTH) AF: 0.368 AC: 22221 AN: 60338

GnomAD4 genome AF: 0.298 AC: 45288 AN: 151820 Hom.: 8004 Cov.: 30 AF XY: 0.303 AC XY: 22442 AN XY: 74168

African (AFR) AF: 0.106 AC: 4378 AN: 41450

American (AMR) AF: 0.291 AC: 4431 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1443 AN: 5126

South Asian (SAS) AF: 0.478 AC: 2302 AN: 4816

European-Finnish (FIN) AF: 0.378 AC: 3974 AN: 10506

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26018 AN: 67894

Other (OTH) AF: 0.338 AC: 713 AN: 2108

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
PhyloP100		1.3
BranchPoint Hunter		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs858521; hg19: chr17-7530147; COSMIC: COSV52646355; COSMIC: COSV52646355;