17-7627611-C-T

Variant names:

• chr17-7627611-C-T
• rs141081070
• NM_133491.5:c.25G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_133491.5(SAT2):​c.25G>A​(p.Ala9Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A9D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: SAT2 NM_133491.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09133336).

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.25G>A	p.Ala9Thr	missense	Exon 1 of 6	NP_597998.1	Q96F10
	SAT2	NM_001320845.1		c.245G>A	p.Gly82Asp	missense	Exon 1 of 6	NP_001307774.1	Q502X4
	SAT2	NM_001320846.1		c.245G>A	p.Gly82Asp	missense	Exon 1 of 5	NP_001307775.1	Q96F10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAT2	ENST00000269298.10	TSL:1 MANE Select	c.25G>A	p.Ala9Thr	missense	Exon 1 of 6	ENSP00000269298.5	Q96F10
	SHBG	ENST00000575314.5	TSL:1	c.-61-2807C>T		intron	N/A	ENSP00000458559.1	I3L145
	SHBG	ENST00000572262.5	TSL:1	c.-61-2807C>T		intron	N/A	ENSP00000459999.1	I3L2X4

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152114 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000720 AC: 18 AN: 249966 AF XY: 0.0000444

Gnomad AFR exome AF: 0.000741

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461070 Hom.: 0 Cov.: 33 AF XY: 0.0000275 AC XY: 20 AN XY: 726832

African (AFR) AF: 0.000897 AC: 30 AN: 33456

American (AMR) AF: 0.000112 AC: 5 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111648

Other (OTH) AF: 0.0000497 AC: 3 AN: 60356

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152114 Hom.: 0 Cov.: 31 AF XY: 0.000188 AC XY: 14 AN XY: 74298

African (AFR) AF: 0.000942 AC: 39 AN: 41412

American (AMR) AF: 0.0000655 AC: 1 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000119 Hom.: 0

Bravo AF: 0.000359

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.2
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.46
MVP		0.51
MPC		0.91
ClinPred		0.50	T
GERP RS		4.7
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.87
Mutation Taster		=77/23	polymorphism

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: rs141081070; hg19: chr17-7530929;