14-63686184-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_030791.4(SGPP1):​c.1247G>A​(p.Arg416Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000173 in 1,613,450 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

SGPP1
NM_030791.4 missense

Scores

6
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.50
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 -4 ACMG points.

BS2
High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SGPP1NM_030791.4 linkc.1247G>A p.Arg416Gln missense_variant Exon 3 of 3 ENST00000247225.7 NP_110418.1 Q9BX95

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SGPP1ENST00000247225.7 linkc.1247G>A p.Arg416Gln missense_variant Exon 3 of 3 1 NM_030791.4 ENSP00000247225.6 Q9BX95

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
151922
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000947
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000131
AC:
33
AN:
251116
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135722
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000179
AC:
261
AN:
1461528
Hom.:
0
Cov.:
31
AF XY:
0.000177
AC XY:
129
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000209
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
151922
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74160
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000947
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000230
Hom.:
0
Bravo
AF:
0.000162
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.000237

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1247G>A (p.R416Q) alteration is located in exon 3 (coding exon 3) of the SGPP1 gene. This alteration results from a G to A substitution at nucleotide position 1247, causing the arginine (R) at amino acid position 416 to be replaced by a glutamine (Q). 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
0.58
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Pathogenic
0.36
CADD
Uncertain
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.28
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.0083
T
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-0.59
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.43
Sift
Benign
0.035
D
Sift4G
Uncertain
0.016
D
Polyphen
0.97
D
Vest4
0.86
MVP
0.53
MPC
0.55
ClinPred
0.68
D
GERP RS
5.2
Varity_R
0.30
gMVP
0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138943256; hg19: chr14-64152902; COSMIC: COSV55974647; API