NM_002970.4:c.34G>A

Variant names:

• chrX-23783385-G-A
• rs145980431
• NM_002970.4:c.34G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002970.4(SAT1):​c.34G>A​(p.Ala12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,209,304 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 159 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A12D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., 8 hem., cov: 23)
  • Exomes 𝑓: 0.00048 (0 hom. 151 hem.)
• Consequence: SAT1 NM_002970.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86
• Publications: 2 publications found

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]

SAT1-DT (HGNC:56726): (SAT1 divergent transcript)

ENSG00000288706 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051607817).
• BP6: Variant X-23783385-G-A is Benign according to our data. Variant chrX-23783385-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3250627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAT1	NM_002970.4	c.34G>A	p.Ala12Thr	missense_variant	Exon 1 of 6	ENST00000379270.5	NP_002961.1
SAT1	NR_027783.3	n.213G>A		non_coding_transcript_exon_variant	Exon 1 of 7
LOC127933115	NM_001414725.1	c.*18G>A		downstream_gene_variant			NP_001401654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAT1	ENST00000379270.5	c.34G>A	p.Ala12Thr	missense_variant	Exon 1 of 6	1	NM_002970.4	ENSP00000368572.4
ENSG00000288706	ENST00000683890.1	c.*18G>A		downstream_gene_variant				ENSP00000506989.1

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 28 AN: 112178 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000970

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000378

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: 0.000376

Gnomad OTH AF: 0.000657

GnomAD2 exomes AF: 0.000285 AC: 52 AN: 182308 AF XY: 0.000239

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000621

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000419

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000480 AC: 527 AN: 1097074 Hom.: 0 Cov.: 29 AF XY: 0.000417 AC XY: 151 AN XY: 362458

African (AFR) AF: 0.0000758 AC: 2 AN: 26381

American (AMR) AF: 0.000625 AC: 22 AN: 35179

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19378

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.00 AC: 0 AN: 54013

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4083

European-Non Finnish (NFE) AF: 0.000584 AC: 491 AN: 841290

Other (OTH) AF: 0.000239 AC: 11 AN: 46036

GnomAD4 genome AF: 0.000249 AC: 28 AN: 112230 Hom.: 0 Cov.: 23 AF XY: 0.000232 AC XY: 8 AN XY: 34418

African (AFR) AF: 0.0000968 AC: 3 AN: 30985

American (AMR) AF: 0.000377 AC: 4 AN: 10602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3527

South Asian (SAS) AF: 0.00 AC: 0 AN: 2706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6151

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000376 AC: 20 AN: 53167

Other (OTH) AF: 0.000649 AC: 1 AN: 1540

Alfa AF: 0.000327 Hom.: 3

Bravo AF: 0.000412

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000743 AC: 5

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.0000545

EpiControl AF: 0.000475

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SAT1: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;T;.;T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;.;.;L
PhyloP100		1.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.44	N;N;N;N
REVEL	Benign	0.036
Sift	Benign	0.084	T;T;T;T
Sift4G	Benign	0.086	T;T;T;T
Polyphen		0.98, 0.37	.;D;.;B
Vest4		0.22
MVP		0.48
MPC		1.0
ClinPred		0.043	T
GERP RS		3.5
PromoterAI		-0.096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.50
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs145980431; hg19: chrX-23801502; COSMIC: COSV104675186; COSMIC: COSV104675186;