14-63727556-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_030791.4(SGPP1):​c.389G>A​(p.Cys130Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SGPP1
NM_030791.4 missense

Scores

1
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.17
Variant links:
Genes affected
SGPP1 (HGNC:17720): (sphingosine-1-phosphate phosphatase 1) Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that regulates diverse biologic processes. SGPP1 catalyzes the degradation of S1P via salvage and recycling of sphingosine into long-chain ceramides (Mandala et al., 2000 [PubMed 10859351]; Le Stunff et al., 2007 [PubMed 17895250]).[supplied by OMIM, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07061517).
BP6
Variant 14-63727556-C-T is Benign according to our data. Variant chr14-63727556-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2534542.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SGPP1NM_030791.4 linkc.389G>A p.Cys130Tyr missense_variant Exon 1 of 3 ENST00000247225.7 NP_110418.1 Q9BX95

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SGPP1ENST00000247225.7 linkc.389G>A p.Cys130Tyr missense_variant Exon 1 of 3 1 NM_030791.4 ENSP00000247225.6 Q9BX95

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457704
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725102
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Apr 07, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.053
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
16
DANN
Benign
0.94
DEOGEN2
Benign
0.14
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.043
N
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-2.2
N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
6.1
N
REVEL
Benign
0.17
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.25
MutPred
0.58
Gain of catalytic residue at N125 (P = 0);
MVP
0.043
MPC
1.7
ClinPred
0.36
T
GERP RS
0.41
Varity_R
0.091
gMVP
0.64

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: chr14-64194274; API