Variant X-85107620-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.1349T>C(p.Val450Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,208,787 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.0000090 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000023 ( 0 hom. 4 hem. )

Consequence

SATL1
NM_001367857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.99

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=0.039648265).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SATL1	NM_001367857.2 linkuse as main transcript	c.1349T>C	p.Val450Ala	missense_variant	3/8	ENST00000644105.2
SATL1	NM_001367858.2 linkuse as main transcript	c.1349T>C	p.Val450Ala	missense_variant	7/12
SATL1	NM_001012980.2 linkuse as main transcript	c.1349T>C	p.Val450Ala	missense_variant	1/5
SATL1	XM_047442081.1 linkuse as main transcript	c.1349T>C	p.Val450Ala	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATL1	ENST00000644105.2 linkuse as main transcript	c.1349T>C	p.Val450Ala	missense_variant	3/8		NM_001367857.2	A2	Q86VE3-1

Frequencies

GnomAD3 genomes

AF:

0.00000905

AC:

AN:

110535

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33195

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183416

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000228

AC:

AN:

1098252

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363610

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000297

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000905

AC:

AN:

110535

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33195

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000190

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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 17, 2024

The c.1349T>C (p.V450A) 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 1349, causing the valine (V) at amino acid position 450 to be replaced by an alanine (A). 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

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.033

DANN

Benign

0.60

DEOGEN2

Benign

0.0056

T;.;.;.;.

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.34

.;T;T;.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.11

N;N;.;.;.

REVEL

Benign

0.061

Sift

Benign

0.65

T;T;.;.;.

Sift4G

Benign

0.53

T;T;.;.;.

Polyphen

0.051

B;.;.;.;.

Vest4

0.028

MutPred

0.20

Loss of catalytic residue at V263 (P = 0.0423);.;.;.;.;

MVP

0.20

MPC

0.29

ClinPred

0.024

GERP RS

0.92

Varity_R

0.026

gMVP

0.10

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