Genetic Variant SAT1:p.Ala12Ser (chrX-23783385-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002970.4(SAT1):c.34G>T(p.Ala12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,097,075 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A12D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

SAT1
NM_002970.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Publications

2 publications found

Variant links:

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 links:

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

SAT1-DT links:

LOC127933115 (HGNC:0):

LOC127933115 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11799672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002970.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SAT1	NM_002970.4	MANE Select	c.34G>T	p.Ala12Ser	missense	Exon 1 of 6	NP_002961.1
SAT1	NR_027783.3		n.213G>T		non_coding_transcript_exon	Exon 1 of 7
LOC127933115	NM_001414725.1	MANE Select	c.*18G>T		downstream_gene	N/A	NP_001401654.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SAT1	ENST00000379270.5	TSL:1 MANE Select	c.34G>T	p.Ala12Ser	missense	Exon 1 of 6	ENSP00000368572.4
SAT1	ENST00000379254.5	TSL:3	c.34G>T	p.Ala12Ser	missense	Exon 1 of 5	ENSP00000368556.1
SAT1	ENST00000379251.7	TSL:2	n.213G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000549

AC:

AN:

182308

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1097075

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362459

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26381

American (AMR)

AF:

0.00

AC:

AN:

35179

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19378

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

54013

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4083

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841291

Other (OTH)

AF:

0.00

AC:

AN:

46036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

1.9

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.61

REVEL

Benign

0.016

Sift

Benign

0.66

Sift4G

Benign

0.14

Polyphen

0.49

Vest4

0.097

MutPred

0.29

Loss of stability (P = 0.1522)

MVP

0.57

MPC

0.98

ClinPred

0.29

GERP RS

3.5

PromoterAI

-0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.47

Mutation Taster

=90/10

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over