Variant X-85103880-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001367857.2(SATL1):c.1677G>A(p.Met559Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000795 in 1,194,341 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., 16 hem., cov: 23)

Exomes 𝑓: 0.000045 ( 0 hom. 17 hem. )

Consequence

SATL1
NM_001367857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.163

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SATL1	NM_001367857.2 linkuse as main transcript	c.1677G>A	p.Met559Ile	missense_variant	4/8	ENST00000644105.2
SATL1	NM_001367858.2 linkuse as main transcript	c.1677G>A	p.Met559Ile	missense_variant	8/12
SATL1	NM_001012980.2 linkuse as main transcript	c.1677G>A	p.Met559Ile	missense_variant	2/5
SATL1	XM_047442081.1 linkuse as main transcript	c.1677G>A	p.Met559Ile	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATL1	ENST00000644105.2 linkuse as main transcript	c.1677G>A	p.Met559Ile	missense_variant	4/8		NM_001367857.2	A2	Q86VE3-1

Frequencies

GnomAD3 genomes

AF:

0.000403

AC:

AN:

111637

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

33853

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000959

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:

0.000668

GnomAD3 exomes

AF:

0.000104

AC:

AN:

182697

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

67293

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000528

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000453

AC:

AN:

1082650

Hom.:

Cov.:

AF XY:

0.0000486

AC XY:

AN XY:

350144

show subpopulations

Gnomad4 AFR exome

AF:

0.00138

Gnomad4 AMR exome

AF:

0.0000856

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000745

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000412

AC:

AN:

111691

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

AN XY:

33917

show subpopulations

Gnomad4 AFR

AF:

0.00143

Gnomad4 AMR

AF:

0.0000958

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:

0.000659

Alfa

AF:

0.0000597

Hom.:

Bravo

AF:

0.000397

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

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

Sep 26, 2023

The c.1677G>A (p.M559I) alteration is located in exon 2 (coding exon 2) of the SATL1 gene. This alteration results from a G to A substitution at nucleotide position 1677, causing the methionine (M) at amino acid position 559 to be replaced by an isoleucine (I). 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

0.30

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.0029

T;.;.;.;.

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.57

.;T;T;.;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

1.4

N;N;.;.;.

REVEL

Benign

0.042

Sift

Uncertain

0.0090

D;T;.;.;.

Sift4G

Uncertain

0.017

D;D;.;.;.

Polyphen

0.0090

B;.;.;.;.

Vest4

0.084

MutPred

0.58

Loss of stability (P = 0.161);.;.;.;.;

MVP

0.50

MPC

0.10

ClinPred

0.020

GERP RS

3.4

Varity_R

0.22

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.45

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.45

Position offset: -16

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