X-85094935-G-A

Variant names:

• chrX-85094935-G-A
• rs141349825
• NM_001367857.2:c.1755C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001367857.2(SATL1):​c.1755C>T​(p.Asn585Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,178,147 control chromosomes in the GnomAD database, including 254 homozygotes. There are 8,287 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.017 (19 hom., 549 hem., cov: 23)
  • Exomes 𝑓: 0.022 (235 hom. 7738 hem.)
• Consequence: SATL1 NM_001367857.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.19

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-85094935-G-A is Benign according to our data. Variant chrX-85094935-G-A is described in ClinVar as [Benign]. Clinvar id is 3037120.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0168 (1878/111768) while in subpopulation SAS AF= 0.0391 (104/2658). AF 95% confidence interval is 0.033. There are 19 homozygotes in gnomad4. There are 549 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SATL1	NM_001367857.2	c.1755C>T	p.Asn585Asn	synonymous_variant	Exon 5 of 8	ENST00000644105.2	NP_001354786.1
SATL1	NM_001367858.2	c.1755C>T	p.Asn585Asn	synonymous_variant	Exon 9 of 12		NP_001354787.1
SATL1	NM_001012980.2	c.1755C>T	p.Asn585Asn	synonymous_variant	Exon 3 of 5		NP_001012998.2
SATL1	XM_047442081.1	c.1755C>T	p.Asn585Asn	synonymous_variant	Exon 4 of 7		XP_047298037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SATL1	ENST00000644105.2	c.1755C>T	p.Asn585Asn	synonymous_variant	Exon 5 of 8		NM_001367857.2	ENSP00000494345.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 1880 AN: 111715 Hom.: 19 Cov.: 23 AF XY: 0.0162 AC XY: 548 AN XY: 33919

Gnomad AFR AF: 0.00296

Gnomad AMI AF: 0.0959

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.0147

Gnomad MID AF: 0.0378

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0166

GnomAD3 exomes AF: 0.0206 AC: 3500 AN: 169951 Hom.: 34 AF XY: 0.0233 AC XY: 1350 AN XY: 57857

Gnomad AFR exome AF: 0.00216

Gnomad AMR exome AF: 0.00687

Gnomad ASJ exome AF: 0.0544

Gnomad EAS exome AF: 0.000148

Gnomad SAS exome AF: 0.0478

Gnomad FIN exome AF: 0.0155

Gnomad NFE exome AF: 0.0235

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0223 AC: 23763 AN: 1066379 Hom.: 235 Cov.: 24 AF XY: 0.0229 AC XY: 7738 AN XY: 337845

Gnomad4 AFR exome AF: 0.00220

Gnomad4 AMR exome AF: 0.00770

Gnomad4 ASJ exome AF: 0.0521

Gnomad4 EAS exome AF: 0.000166

Gnomad4 SAS exome AF: 0.0480

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.0223

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0168 AC: 1878 AN: 111768 Hom.: 19 Cov.: 23 AF XY: 0.0162 AC XY: 549 AN XY: 33982

Gnomad4 AFR AF: 0.00295

Gnomad4 AMR AF: 0.00948

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0391

Gnomad4 FIN AF: 0.0147

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0164

Alfa AF: 0.0256 Hom.: 249

Bravo AF: 0.0153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SATL1-related disorder Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141349825; hg19: chrX-84349941;