chrX-85107782-A-G

Position:

• chrX-85107782-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001367857.2(SATL1):​c.1187T>C​(p.Met396Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,221 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 3 hem.)
• Consequence: SATL1 NM_001367857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.70

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04284036).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SATL1	NM_001367857.2	c.1187T>C	p.Met396Thr	missense_variant	3/8	ENST00000644105.2	NP_001354786.1
SATL1	NM_001367858.2	c.1187T>C	p.Met396Thr	missense_variant	7/12		NP_001354787.1
SATL1	NM_001012980.2	c.1187T>C	p.Met396Thr	missense_variant	1/5		NP_001012998.2
SATL1	XM_047442081.1	c.1187T>C	p.Met396Thr	missense_variant	2/7		XP_047298037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SATL1	ENST00000644105.2	c.1187T>C	p.Met396Thr	missense_variant	3/8		NM_001367857.2	ENSP00000494345.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1098221 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 3 AN XY: 363575

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: 0.00000356

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

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

Nov 29, 2024

The c.1187T>C (p.M396T) alteration is located in exon 1 (coding exon 1) of the SATL1 gene. This alteration results from a T to C substitution at nucleotide position 1187, causing the methionine (M) at amino acid position 396 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	Benign	0.13
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.039
DANN	Benign	0.50
DEOGEN2	Benign	0.0043	T;.;.;.;.
FATHMM_MKL	Benign	0.0087	N
LIST_S2	Benign	0.27	.;T;T;.;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.043	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.91	L;.;.;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.1	N;N;.;.;.
REVEL	Benign	0.017
Sift	Benign	0.19	T;T;.;.;.
Sift4G	Benign	0.62	T;T;.;.;.
Polyphen		0.018	B;.;.;.;.
Vest4		0.071
MutPred		0.20		Gain of phosphorylation at M209 (P = 0.0276);.;.;.;.;
MVP		0.17
MPC		0.062
ClinPred		0.052	T
GERP RS		-5.9
Varity_R		0.072
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-84362788;