Variant X-85107525-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001367857.2(SATL1):c.1444T>C(p.Trp482Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,209,775 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 4 hem., cov: 25)

Exomes 𝑓: 0.000018 ( 0 hom. 3 hem. )

Consequence

SATL1
NM_001367857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.217

Variant links:

Genes affected

SATL1 (HGNC:27992): (spermidine/spermine N1-acetyl transferase like 1) Predicted to enable N-acetyltransferase activity. [provided by Alliance of Genome Resources, Apr 2022]

SATL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012323856).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SATL1	NM_001367857.2 linkuse as main transcript	c.1444T>C	p.Trp482Arg	missense_variant	3/8	ENST00000644105.2
SATL1	NM_001367858.2 linkuse as main transcript	c.1444T>C	p.Trp482Arg	missense_variant	7/12
SATL1	NM_001012980.2 linkuse as main transcript	c.1444T>C	p.Trp482Arg	missense_variant	1/5
SATL1	XM_047442081.1 linkuse as main transcript	c.1444T>C	p.Trp482Arg	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATL1	ENST00000644105.2 linkuse as main transcript	c.1444T>C	p.Trp482Arg	missense_variant	3/8		NM_001367857.2	A2	Q86VE3-1

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

111504

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33976

show subpopulations

Gnomad AFR

AF:

0.000785

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000940

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

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

183346

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67810

show subpopulations

Gnomad AFR exome

AF:

0.000836

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000182

AC:

AN:

1098217

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363577

show subpopulations

Gnomad4 AFR exome

AF:

0.000606

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.000224

AC:

AN:

111558

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

34036

show subpopulations

Gnomad4 AFR

AF:

0.000783

Gnomad4 AMR

AF:

0.0000939

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000287

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2024

The c.1444T>C (p.W482R) alteration is located in exon 1 (coding exon 1) of the SATL1 gene. This alteration results from a T to C substitution at nucleotide position 1444, causing the tryptophan (W) at amino acid position 482 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.46

DANN

Benign

0.40

DEOGEN2

Benign

0.0047

T;.;.;.;.

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.21

.;T;T;.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.36

N;N;.;.;.

REVEL

Benign

0.031

Sift

Benign

0.17

T;T;.;.;.

Sift4G

Benign

0.26

T;T;.;.;.

Polyphen

0.54

P;.;.;.;.

Vest4

0.14

MutPred

0.21

Gain of methylation at W295 (P = 0.0672);.;.;.;.;

MVP

0.29

MPC

0.45

ClinPred

0.0084

GERP RS

-1.5

Varity_R

0.064

gMVP

0.12

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