chrX-23783386-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002970.4(SAT1):c.35C>A(p.Ala12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000458 in 1,209,544 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 158 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A12T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., 8 hem., cov: 23)

Exomes 𝑓: 0.00048 ( 0 hom. 150 hem. )

Consequence

SAT1
NM_002970.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.396

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:

ENSG00000288706 (HGNC:):

ENSG00000288706 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037585407).

BP6

Variant X-23783386-C-A is Benign according to our data. Variant chrX-23783386-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3157918.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAT1	NM_002970.4 link	c.35C>A	p.Ala12Asp	missense_variant	Exon 1 of 6	ENST00000379270.5	NP_002961.1	P21673A0A384NQ10
SAT1	NR_027783.3 link	n.214C>A		non_coding_transcript_exon_variant	Exon 1 of 7
LOC127933115	NM_001414725.1 link	c.*19C>A		downstream_gene_variant			NP_001401654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAT1	ENST00000379270.5 link	c.35C>A	p.Ala12Asp	missense_variant	Exon 1 of 6	1	NM_002970.4	ENSP00000368572.4		P21673
ENSG00000288706	ENST00000683890.1 link	c.*19C>A		downstream_gene_variant				ENSP00000506989.1		A0A804HIB5

Frequencies

GnomAD3 genomes

AF:

0.000249

AC:

AN:

112232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000377

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:

0.000376

Gnomad OTH

AF:

0.000657

GnomAD2 exomes

AF:

0.000280

AC:

AN:

182404

AF XY:

0.000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000621

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000406

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000479

AC:

526

AN:

1097260

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

150

AN XY:

362632

show subpopulations

African (AFR)

AF:

0.0000758

AC:

AN:

26386

American (AMR)

AF:

0.000625

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30200

South Asian (SAS)

AF:

0.00

AC:

AN:

54032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4079

European-Non Finnish (NFE)

AF:

0.000584

AC:

491

AN:

841428

Other (OTH)

AF:

0.000217

AC:

AN:

46052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000249

AC:

AN:

112284

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34468

show subpopulations

African (AFR)

AF:

0.0000968

AC:

AN:

30983

American (AMR)

AF:

0.000377

AC:

AN:

10619

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2657

East Asian (EAS)

AF:

0.00

AC:

AN:

3535

South Asian (SAS)

AF:

0.00

AC:

AN:

2706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6165

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000376

AC:

AN:

53182

Other (OTH)

AF:

0.000649

AC:

AN:

1540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000254

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000475

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.35C>A (p.A12D) alteration is located in exon 1 (coding exon 1) of the SAT1 gene. This alteration results from a C to A substitution at nucleotide position 35, causing the alanine (A) at amino acid position 12 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SAT1: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

T;T;.;T

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.82

.;.;.;L

PhyloP100

0.40

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.86

N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.091

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.27, 0.0010

.;B;.;B

Vest4

0.17

MVP

0.33

MPC

1.5

ClinPred

0.020

GERP RS

1.1

PromoterAI

0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.43

gMVP

0.70

Mutation Taster

=93/7

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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chrX-23783386-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over