Variant X-85103893-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.1664T>C(p.Met555Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,192,110 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000021 ( 0 hom. 11 hem. )

Consequence

SATL1
NM_001367857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.452

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=0.09264827).

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SATL1	NM_001367857.2 linkuse as main transcript	c.1664T>C	p.Met555Thr	missense_variant	4/8	ENST00000644105.2	NP_001354786.1
SATL1	NM_001367858.2 linkuse as main transcript	c.1664T>C	p.Met555Thr	missense_variant	8/12		NP_001354787.1
SATL1	NM_001012980.2 linkuse as main transcript	c.1664T>C	p.Met555Thr	missense_variant	2/5		NP_001012998.2	Q86VE3-2
SATL1	XM_047442081.1 linkuse as main transcript	c.1664T>C	p.Met555Thr	missense_variant	3/7		XP_047298037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SATL1	ENST00000644105.2 linkuse as main transcript	c.1664T>C	p.Met555Thr	missense_variant	4/8		NM_001367857.2	ENSP00000494345.1		Q86VE3-1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

111794

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34010

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182638

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67226

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:

0.0000491

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1080316

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

347606

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:

0.0000266

Gnomad4 OTH exome

AF:

0.0000220

GnomAD4 genome

AF:

0.0000268

AC:

AN:

111794

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34010

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:

0.0000565

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.000119

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

Jul 06, 2024

The c.1664T>C (p.M555T) alteration is located in exon 2 (coding exon 2) of the SATL1 gene. This alteration results from a T to C substitution at nucleotide position 1664, causing the methionine (M) at amino acid position 555 to be replaced by a threonine (T). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.34

DEOGEN2

Benign

0.057

T;.;.;.;.

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.49

.;T;T;.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.093

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.7

M;.;.;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.4

D;N;.;.;.

REVEL

Benign

0.11

Sift

Benign

0.27

T;T;.;.;.

Sift4G

Benign

0.17

T;T;.;.;.

Polyphen

0.052

B;.;.;.;.

Vest4

0.32

MVP

0.65

MPC

0.080

ClinPred

0.14

GERP RS

-1.7

Varity_R

0.19

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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