X-85094987-C-G

Variant names:

• chrX-85094987-C-G
• rs1924657723
• NM_001367857.2:c.1703G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001367857.2(SATL1):​c.1703G>C​(p.Arg568Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,107,175 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 4 hem.)
• Consequence: SATL1 NM_001367857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30474365).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367857.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATL1	NM_001367857.2	MANE Select	c.1703G>C	p.Arg568Thr	missense	Exon 5 of 8	NP_001354786.1	Q86VE3-1
	SATL1	NM_001367858.2		c.1703G>C	p.Arg568Thr	missense	Exon 9 of 12	NP_001354787.1	A0A2R8YFQ0
	SATL1	NM_001012980.2		c.1703G>C	p.Arg568Thr	missense	Exon 3 of 5	NP_001012998.2	Q86VE3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SATL1	ENST00000644105.2	MANE Select	c.1703G>C	p.Arg568Thr	missense	Exon 5 of 8	ENSP00000494345.1	Q86VE3-1
	SATL1	ENST00000509231.1	TSL:1	c.1703G>C	p.Arg568Thr	missense	Exon 3 of 5	ENSP00000425421.1	Q86VE3-2
	SATL1	ENST00000646118.1		c.1703G>C	p.Arg568Thr	missense	Exon 10 of 13	ENSP00000493598.1	Q86VE3-1

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111741 Hom.: 0 Cov.: 23

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: 0.0000111 AC: 11 AN: 995434 Hom.: 0 Cov.: 20 AF XY: 0.0000143 AC XY: 4 AN XY: 280264

African (AFR) AF: 0.00 AC: 0 AN: 24779

American (AMR) AF: 0.00 AC: 0 AN: 34388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18254

East Asian (EAS) AF: 0.00 AC: 0 AN: 29725

South Asian (SAS) AF: 0.00 AC: 0 AN: 49759

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39659

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3891

European-Non Finnish (NFE) AF: 0.0000146 AC: 11 AN: 752381

Other (OTH) AF: 0.00 AC: 0 AN: 42598

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111741 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33931

African (AFR) AF: 0.00 AC: 0 AN: 30711

American (AMR) AF: 0.00 AC: 0 AN: 10499

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6025

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53213

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.065	T
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.1
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.11
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.016	D
Polyphen		0.98	D
Vest4		0.33
MutPred		0.48		Loss of stability (P = 0.1243)
MVP		0.56
MPC		0.15
ClinPred		0.90	D
GERP RS		3.3
Varity_R		0.35
gMVP		0.27
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1924657723; hg19: chrX-84349993;