chr17-7626953-C-A

Variant names:

• chr17-7626953-C-A
• rs858520
• NM_133491.5:c.294G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_133491.5(SAT2):​c.294G>T​(p.Pro98Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: SAT2 NM_133491.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.25
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-6.25 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAT2	NM_133491.5	MANE Select	c.294G>T	p.Pro98Pro	synonymous	Exon 4 of 6	NP_597998.1
	SAT2	NM_001320845.1		c.531G>T	p.Pro177Pro	synonymous	Exon 4 of 6	NP_001307774.1
	SHBG	NM_001289114.2		c.-61-3465C>A		intron	N/A	NP_001276043.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAT2	ENST00000269298.10	TSL:1 MANE Select	c.294G>T	p.Pro98Pro	synonymous	Exon 4 of 6	ENSP00000269298.5
	SHBG	ENST00000575314.5	TSL:1	c.-61-3465C>A		intron	N/A	ENSP00000458559.1
	SHBG	ENST00000572262.5	TSL:1	c.-61-3465C>A		intron	N/A	ENSP00000459999.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		-6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs858520; hg19: chr17-7530271;