X-23783890-C-T

Variant names:

• chrX-23783890-C-T
• rs200440143
• NM_002970.4:c.202+7C>T

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.202+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000814 in 1,209,467 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 311 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., 26 hem., cov: 23)
  • Exomes 𝑓: 0.00083 (0 hom. 285 hem.)
• Consequence: SAT1 NM_002970.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001458
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.498

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004434705).
• BP6: Variant X-23783890-C-T is Benign according to our data. Variant chrX-23783890-C-T is described in ClinVar as [Benign]. Clinvar id is 747117.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAT1	NM_002970.4	c.202+7C>T		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000379270.5	NP_002961.1
SAT1	NR_027783.3	n.381+7C>T		splice_region_variant, intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAT1	ENST00000379270.5	c.202+7C>T		splice_region_variant, intron_variant	Intron 3 of 5	1	NM_002970.4	ENSP00000368572.4

Frequencies

GnomAD3 genomes AF: 0.000684 AC: 76 AN: 111175 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000196

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: 0.00287

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000545 AC: 100 AN: 183418 AF XY: 0.000486

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00250

Gnomad NFE exome AF: 0.000647

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.000828 AC: 909 AN: 1098236 Hom.: 0 Cov.: 33 AF XY: 0.000784 AC XY: 285 AN XY: 363594

Gnomad4 AFR exome AF: 0.000114 AC: 3 AN: 26403

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 35204

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 19385

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 30205

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 54142

Gnomad4 FIN exome AF: 0.00296 AC: 120 AN: 40524

Gnomad4 NFE exome AF: 0.000908 AC: 765 AN: 842139

Gnomad4 Remaining exome AF: 0.000456 AC: 21 AN: 46097

GnomAD4 genome AF: 0.000683 AC: 76 AN: 111231 Hom.: 0 Cov.: 23 AF XY: 0.000777 AC XY: 26 AN XY: 33459

Gnomad4 AFR AF: 0.000196 AC: 0.000195746 AN: 0.000195746

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00287 AC: 0.00286968 AN: 0.00286968

Gnomad4 NFE AF: 0.00100 AC: 0.000999623 AN: 0.000999623

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.000797 Hom.: 7

Bravo AF: 0.000400

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000692 AC: 2

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000892 AC: 6

ExAC AF: 0.000502 AC: 61

EpiCase AF: 0.000436

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 07, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	8.3
DANN	Benign	0.95
DEOGEN2	Benign	0.0058	T;T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.0044	T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	2.2	N;N
REVEL	Benign	0.066
Sift	Uncertain	0.0070	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.017	.;B
Vest4		0.13
MVP		0.17
ClinPred		0.016	T
GERP RS		-0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.044
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: rs200440143; hg19: chrX-23802007;