X-85094947-A-C

Position:

• chrX-85094947-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001367857.2(SATL1):​c.1743T>G​(p.Ile581Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SATL1 NM_001367857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.402

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32245398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SATL1	NM_001367857.2	c.1743T>G	p.Ile581Met	missense_variant	5/8	ENST00000644105.2
SATL1	NM_001367858.2	c.1743T>G	p.Ile581Met	missense_variant	9/12
SATL1	NM_001012980.2	c.1743T>G	p.Ile581Met	missense_variant	3/5
SATL1	XM_047442081.1	c.1743T>G	p.Ile581Met	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATL1	ENST00000644105.2	c.1743T>G	p.Ile581Met	missense_variant	5/8		NM_001367857.2	A2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.1743T>G (p.I581M) alteration is located in exon 3 (coding exon 3) of the SATL1 gene. This alteration results from a T to G substitution at nucleotide position 1743, causing the isoleucine (I) at amino acid position 581 to be replaced by a methionine (M). 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	0.24
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T;.;.;.;.
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.67	.;T;T;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.3	M;.;.;.;.
MutationTaster	Benign	0.90	N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N;N;.;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D;.;.;.
Sift4G	Uncertain	0.0030	D;D;.;.;.
Polyphen		1.0	D;.;.;.;.
Vest4		0.43
MutPred		0.63		Gain of disorder (P = 0.0669);.;.;.;.;
MVP		0.40
MPC		0.21
ClinPred		0.89	D
GERP RS		2.9
Varity_R		0.47
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1924655073; hg19: chrX-84349953;