rs104894035

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004577.4(PSPH):​c.94G>A​(p.Asp32Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000474 in 152,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D32G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 36)
Exomes 𝑓: 0.000024 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PSPH
NM_004577.4 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:2

Conservation

PhyloP100: 6.00
Variant links:
Genes affected
PSPH (HGNC:9577): (phosphoserine phosphatase) The protein encoded by this gene belongs to a subfamily of the phosphotransferases. This encoded enzyme is responsible for the third and last step in L-serine formation. It catalyzes magnesium-dependent hydrolysis of L-phosphoserine and is also involved in an exchange reaction between L-serine and L-phosphoserine. Deficiency of this protein is thought to be linked to Williams syndrome. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0996795).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PSPHNM_004577.4 linkuse as main transcriptc.94G>A p.Asp32Asn missense_variant 4/8 ENST00000275605.8 NP_004568.2 P78330A0A024RDL3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PSPHENST00000275605.8 linkuse as main transcriptc.94G>A p.Asp32Asn missense_variant 4/81 NM_004577.4 ENSP00000275605.3 P78330

Frequencies

GnomAD3 genomes
AF:
0.000474
AC:
72
AN:
151882
Hom.:
0
Cov.:
36
show subpopulations
Gnomad AFR
AF:
0.00148
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251428
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000239
AC:
35
AN:
1461480
Hom.:
0
Cov.:
33
AF XY:
0.0000330
AC XY:
24
AN XY:
727056
show subpopulations
Gnomad4 AFR exome
AF:
0.000482
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000474
AC:
72
AN:
152000
Hom.:
0
Cov.:
36
AF XY:
0.000471
AC XY:
35
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00148
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000563
Hom.:
0
ExAC
AF:
0.000173
AC:
21

ClinVar

Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Deficiency of phosphoserine phosphatase Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsMay 11, 2018This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -
Pathogenic, no assertion criteria providedliterature onlyOMIMFeb 01, 2004- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;D;D;T;T
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.16
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
.;D;D;.;D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.10
T;T;T;T;T
MetaSVM
Pathogenic
0.90
D
MutationAssessor
Pathogenic
3.1
M;M;.;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-4.5
D;D;D;D;D
REVEL
Pathogenic
0.66
Sift
Benign
0.033
D;D;D;D;D
Sift4G
Uncertain
0.031
D;D;.;.;.
Polyphen
0.99
D;D;.;.;.
Vest4
0.93
MVP
0.91
MPC
0.79
ClinPred
0.94
D
GERP RS
4.7
Varity_R
0.69
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs104894035; hg19: chr7-56088812; COSMIC: COSV51909126; COSMIC: COSV51909126; API