chrX-85103876-A-T

Position:

• chrX-85103876-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367857.2(SATL1):​c.1681T>A​(p.Leu561Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000926 in 1,080,230 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: SATL1 NM_001367857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.149

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10850832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SATL1	NM_001367857.2	c.1681T>A	p.Leu561Ile	missense_variant	4/8	ENST00000644105.2
SATL1	NM_001367858.2	c.1681T>A	p.Leu561Ile	missense_variant	8/12
SATL1	NM_001012980.2	c.1681T>A	p.Leu561Ile	missense_variant	2/5
SATL1	XM_047442081.1	c.1681T>A	p.Leu561Ile	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SATL1	ENST00000644105.2	c.1681T>A	p.Leu561Ile	missense_variant	4/8		NM_001367857.2	A2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.26e-7 AC: 1 AN: 1080230 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 348112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000335

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 Cov.: 23

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

May 03, 2023

The c.1681T>A (p.L561I) alteration is located in exon 2 (coding exon 2) of the SATL1 gene. This alteration results from a T to A substitution at nucleotide position 1681, causing the leucine (L) at amino acid position 561 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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.91
DEOGEN2	Benign	0.0053	T;.;.;.;.
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.73	.;T;T;.;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.29	N;N;.;.;.
REVEL	Benign	0.030
Sift	Benign	0.17	T;D;.;.;.
Sift4G	Benign	0.13	T;T;.;.;.
Polyphen		0.051	B;.;.;.;.
Vest4		0.23
MutPred		0.43		Gain of catalytic residue at L379 (P = 0.0803);.;.;.;.;
MVP		0.52
MPC		0.12
ClinPred		0.11	T
GERP RS		-0.32
Varity_R		0.091
gMVP		0.090

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-84358882;