Genetic Variant SATL1:p.Tyr602His (chrX-85094200-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001367857.2(SATL1):c.1804T>C(p.Tyr602His) variant causes a missense change. The variant allele was found at a frequency of 0.0000152 in 1,183,485 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 3 hem. )

Consequence

SATL1
NM_001367857.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65

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 GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATL1	NM_001367857.2 link	c.1804T>C	p.Tyr602His	missense_variant	Exon 6 of 8	ENST00000644105.2	NP_001354786.1
SATL1	NM_001367858.2 link	c.1804T>C	p.Tyr602His	missense_variant	Exon 10 of 12		NP_001354787.1
SATL1	NM_001012980.2 link	c.1804T>C	p.Tyr602His	missense_variant	Exon 4 of 5		NP_001012998.2	Q86VE3-2
SATL1	XM_047442081.1 link	c.1804T>C	p.Tyr602His	missense_variant	Exon 5 of 7		XP_047298037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SATL1	ENST00000644105.2 link	c.1804T>C	p.Tyr602His	missense_variant	Exon 6 of 8		NM_001367857.2	ENSP00000494345.1		Q86VE3-1

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33942

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1071697

Hom.:

Cov.:

AF XY:

0.00000883

AC XY:

AN XY:

339639

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:

0.0000208

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33942

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1804T>C (p.Y602H) 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 1804, causing the tyrosine (Y) at amino acid position 602 to be replaced by a histidine (H). 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

0.70

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.083

T;.;.;.;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

.;D;D;.;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.61

D;D;D;D;D

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.9

M;.;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.4

D;N;.;.;.

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;.;.;.

Sift4G

Pathogenic

0.0

D;D;.;.;.

Polyphen

1.0

D;.;.;.;.

Vest4

0.53

MutPred

0.77

Gain of sheet (P = 0.0827);.;.;.;.;

MVP

0.64

MPC

0.20

ClinPred

1.0

GERP RS

4.1

Varity_R

0.72

gMVP

0.33

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