17-7626584-G-A

Variant names:

• chr17-7626584-G-A
• rs13894
• NM_133491.5:c.376C>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.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.

• Frequency:
  • Genomes: 𝑓 0.071 (387 hom., cov: 31)
  • Exomes 𝑓: 0.074 (4170 hom.)
• Consequence: SAT2 NM_133491.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 49 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: 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133491.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAT2	NM_133491.5	MANE Select	c.376C>T	p.Arg126Cys	missense	Exon 6 of 6	NP_597998.1
	SAT2	NM_001320845.1		c.613C>T	p.Arg205Cys	missense	Exon 6 of 6	NP_001307774.1
	SAT2	NM_001320846.1		c.511C>T	p.Arg171Cys	missense	Exon 5 of 5	NP_001307775.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAT2	ENST00000269298.10	TSL:1 MANE Select	c.376C>T	p.Arg126Cys	missense	Exon 6 of 6	ENSP00000269298.5
	SAT2	ENST00000380466.6	TSL:1	n.627C>T		non_coding_transcript_exon	Exon 6 of 6
	SHBG	ENST00000575314.5	TSL:1	c.-61-3834G>A		intron	N/A	ENSP00000458559.1

Frequencies

GnomAD3 genomes AF: 0.0713 AC: 10856 AN: 152158 Hom.: 384 Cov.: 31

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

GnomAD2 exomes AF: 0.0695 AC: 17433 AN: 250946 AF XY: 0.0717

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 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.: 32 AF XY: 0.0749 AC XY: 54427 AN XY: 727120

African (AFR) AF: 0.0807 AC: 2701 AN: 33476

American (AMR) AF: 0.0399 AC: 1784 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 2339 AN: 26116

East Asian (EAS) AF: 0.0540 AC: 2142 AN: 39694

South Asian (SAS) AF: 0.108 AC: 9354 AN: 86226

European-Finnish (FIN) AF: 0.0534 AC: 2853 AN: 53416

Middle Eastern (MID) AF: 0.0501 AC: 289 AN: 5766

European-Non Finnish (NFE) AF: 0.0733 AC: 81534 AN: 1111884

Other (OTH) AF: 0.0762 AC: 4600 AN: 60382

GnomAD4 genome AF: 0.0713 AC: 10863 AN: 152276 Hom.: 387 Cov.: 31 AF XY: 0.0702 AC XY: 5224 AN XY: 74448

African (AFR) AF: 0.0761 AC: 3163 AN: 41554

American (AMR) AF: 0.0552 AC: 844 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 310 AN: 3472

East Asian (EAS) AF: 0.0434 AC: 225 AN: 5186

South Asian (SAS) AF: 0.107 AC: 517 AN: 4822

European-Finnish (FIN) AF: 0.0554 AC: 588 AN: 10610

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5006 AN: 68020

Other (OTH) AF: 0.0692 AC: 146 AN: 2110

Alfa AF: 0.0724 Hom.: 1667

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.8
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.39
MPC		1.3
ClinPred		0.024	T
GERP RS		4.2
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.57
gMVP		0.60
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13894; hg19: chr17-7529902; COSMIC: COSV52647775; COSMIC: COSV52647775;