rs11550721

Variant names:

• chrX-23783194-C-T
• rs11550721
• NM_002970.4:c.-158C>T

Variant summary

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

The NM_002970.4(SAT1):​c.-158C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 492,990 control chromosomes in the GnomAD database, including 8,542 homozygotes. There are 30,372 hemizygotes in GnomAD. 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 0.17 (1592 hom., 5396 hem., cov: 23)
  • Exomes 𝑓: 0.21 (6950 hom. 24976 hem.)
• Consequence: SAT1 NM_002970.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 4 publications found

Genes affected

SAT1 (HGNC:10540): (spermidine/spermine N1-acetyltransferase 1) The protein encoded by this gene belongs to the acetyltransferase family, and is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the acetylation of spermidine and spermine, and is involved in the regulation of the intracellular concentration of polyamines and their transport out of cells. Defects in this gene are associated with keratosis follicularis spinulosa decalvans (KFSD). Alternatively spliced transcripts have been found for this gene.[provided by RefSeq, Sep 2009]

SAT1-DT (HGNC:56726): (SAT1 divergent transcript)

ENSG00000288706 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAT1	NM_002970.4	c.-158C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000379270.5	NP_002961.1
SAT1	NM_002970.4	c.-158C>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000379270.5	NP_002961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAT1	ENST00000379270.5	c.-158C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_002970.4	ENSP00000368572.4
SAT1	ENST00000379270.5	c.-158C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_002970.4	ENSP00000368572.4
ENSG00000288706	ENST00000683890.1	c.-84C>T		upstream_gene_variant				ENSP00000506989.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 18744 AN: 111404 Hom.: 1591 Cov.: 23

Gnomad AFR AF: 0.0369

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.000843

Gnomad SAS AF: 0.0428

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.0798

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.208 AC: 79322 AN: 381535 Hom.: 6950 Cov.: 5 AF XY: 0.201 AC XY: 24976 AN XY: 124315

African (AFR) AF: 0.0362 AC: 410 AN: 11338

American (AMR) AF: 0.0936 AC: 1982 AN: 21170

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 2379 AN: 11971

East Asian (EAS) AF: 0.000257 AC: 6 AN: 23350

South Asian (SAS) AF: 0.0539 AC: 1743 AN: 32320

European-Finnish (FIN) AF: 0.284 AC: 9934 AN: 34965

Middle Eastern (MID) AF: 0.127 AC: 275 AN: 2160

European-Non Finnish (NFE) AF: 0.262 AC: 58401 AN: 222939

Other (OTH) AF: 0.197 AC: 4192 AN: 21322

GnomAD4 genome AF: 0.168 AC: 18749 AN: 111455 Hom.: 1592 Cov.: 23 AF XY: 0.160 AC XY: 5396 AN XY: 33667

African (AFR) AF: 0.0368 AC: 1136 AN: 30878

American (AMR) AF: 0.122 AC: 1289 AN: 10540

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 531 AN: 2637

East Asian (EAS) AF: 0.000845 AC: 3 AN: 3549

South Asian (SAS) AF: 0.0441 AC: 120 AN: 2724

European-Finnish (FIN) AF: 0.278 AC: 1636 AN: 5882

Middle Eastern (MID) AF: 0.0876 AC: 19 AN: 217

European-Non Finnish (NFE) AF: 0.257 AC: 13592 AN: 52850

Other (OTH) AF: 0.154 AC: 234 AN: 1517

Alfa AF: 0.212 Hom.: 8962

Bravo AF: 0.152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.9
DANN	Benign	0.80
PhyloP100		-2.0
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	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: rs11550721; hg19: chrX-23801311;