X-23783386-C-A

Position:

chrX-23783386-C-A

Variant summary

Our verdict is Benign. Variant got -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. 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

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:

LOC127933115 (HGNC:):

LOC127933115 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SAT1	NM_002970.4 linkuse as main transcript	c.35C>A	p.Ala12Asp	missense_variant	1/6	ENST00000379270.5
SAT1	NR_027783.3 linkuse as main transcript	n.214C>A		non_coding_transcript_exon_variant	1/7
LOC127933115	NM_001414725.1 linkuse as main transcript			downstream_gene_variant		ENST00000683890.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAT1	ENST00000379270.5 linkuse as main transcript	c.35C>A	p.Ala12Asp	missense_variant	1/6	1	NM_002970.4	P1
	ENST00000683890.1 linkuse as main transcript			downstream_gene_variant			NM_001414725.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000249

AC:

AN:

112232

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

AN XY:

34406

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

GnomAD3 exomes

AF:

0.000280

AC:

AN:

182404

Hom.:

AF XY:

0.000224

AC XY:

AN XY:

66998

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000249

AC:

AN:

112284

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

34468

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.000377

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000376

Gnomad4 OTH

AF:

0.000649

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2022

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

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

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

MutationTaster

Benign

0.81

N;N;N;N

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.43

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over