X-23783398-A-T

Variant names:

• chrX-23783398-A-T
• NM_002970.4:c.47A>T

Variant summary

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

The NM_002970.4(SAT1):​c.47A>T​(p.Asp16Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SAT1 NM_002970.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.19

Genes affected

SAT1 (HGNC:10540): (spermidine/spermine N1-acetyltransferase 1) The protein encoded by this gene belongs to the acetyltransferase family, and is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the acetylation of spermidine and spermine, and is involved in the regulation of the intracellular concentration of polyamines and their transport out of cells. Defects in this gene are associated with keratosis follicularis spinulosa decalvans (KFSD). Alternatively spliced transcripts have been found for this gene.[provided by RefSeq, Sep 2009]

ENSG00000288706 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAT1	NM_002970.4	c.47A>T	p.Asp16Val	missense_variant	Exon 1 of 6	ENST00000379270.5	NP_002961.1
SAT1	NR_027783.3	n.226A>T		non_coding_transcript_exon_variant	Exon 1 of 7
LOC127933115	NM_001414725.1	c.*31A>T		downstream_gene_variant			NP_001401654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAT1	ENST00000379270.5	c.47A>T	p.Asp16Val	missense_variant	Exon 1 of 6	1	NM_002970.4	ENSP00000368572.4
ENSG00000288706	ENST00000683890.1	c.*31A>T		downstream_gene_variant				ENSP00000506989.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.47A>T (p.D16V) alteration is located in exon 1 (coding exon 1) of the SAT1 gene. This alteration results from a A to T substitution at nucleotide position 47, causing the aspartic acid (D) at amino acid position 16 to be replaced by a valine (V). 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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.6	.;.;.;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-5.6	D;D;D;D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;T;D
Polyphen		1.0, 1.0	.;D;.;D
Vest4		0.67
MutPred		0.45		Gain of MoRF binding (P = 0.0699);Gain of MoRF binding (P = 0.0699);Gain of MoRF binding (P = 0.0699);Gain of MoRF binding (P = 0.0699);
MVP		0.94
MPC		2.6
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.91
gMVP		0.97

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-23801515;