Variant chrX-85094152-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367857.2(SATL1):c.1852T>C(p.Phe618Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000153 in 1,176,700 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.0000047 ( 0 hom. 2 hem. )

Consequence

SATL1
NM_001367857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21777156).

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SATL1	NM_001367857.2 linkuse as main transcript	c.1852T>C	p.Phe618Leu	missense_variant	6/8	ENST00000644105.2
SATL1	NM_001367858.2 linkuse as main transcript	c.1852T>C	p.Phe618Leu	missense_variant	10/12
SATL1	NM_001012980.2 linkuse as main transcript	c.1852T>C	p.Phe618Leu	missense_variant	4/5
SATL1	XM_047442081.1 linkuse as main transcript	c.1852T>C	p.Phe618Leu	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATL1	ENST00000644105.2 linkuse as main transcript	c.1852T>C	p.Phe618Leu	missense_variant	6/8		NM_001367857.2	A2	Q86VE3-1

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

111544

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

AN XY:

33700

show subpopulations

Gnomad AFR

AF:

0.000424

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

180954

Hom.:

AF XY:

0.0000458

AC XY:

AN XY:

65488

show subpopulations

Gnomad AFR exome

AF:

0.000381

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:

0.00000469

AC:

AN:

1065156

Hom.:

Cov.:

AF XY:

0.00000594

AC XY:

AN XY:

336448

show subpopulations

Gnomad4 AFR exome

AF:

0.000194

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:

0.00

GnomAD4 genome

AF:

0.000117

AC:

AN:

111544

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

AN XY:

33700

show subpopulations

Gnomad4 AFR

AF:

0.000424

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000125

ExAC

AF:

0.0000330

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

Jan 27, 2022

The c.1852T>C (p.F618L) alteration is located in exon 4 (coding exon 4) of the SATL1 gene. This alteration results from a T to C substitution at nucleotide position 1852, causing the phenylalanine (F) at amino acid position 618 to be replaced by a leucine (L). 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;.;.;.;.

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.95

.;D;D;.;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;.;.;.;.

MutationTaster

Benign

0.64

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.1

D;N;.;.;.

REVEL

Benign

0.15

Sift

Benign

0.087

T;D;.;.;.

Sift4G

Benign

0.27

T;T;.;.;.

Polyphen

0.96

P;.;.;.;.

Vest4

0.36

MutPred

0.55

Gain of sheet (P = 0.039);.;.;.;.;

MVP

0.40

MPC

0.067

ClinPred

0.34

GERP RS

5.1

Varity_R

0.29

gMVP

0.28

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