7-56011767-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004577.4(PSPH):c.673G>A(p.Glu225Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,609,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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. E225Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

PSPH
NM_004577.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 2.20

Publications

0 publications found

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]

PSPH Gene-Disease associations (from GenCC):

Neu-Laxova syndrome 1
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
PSPH deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
neurometabolic disorder due to serine deficiency
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

PSPH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029164135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004577.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSPH	NM_004577.4	MANE Select	c.673G>A	p.Glu225Lys	missense	Exon 8 of 8	NP_004568.2
PSPH	NM_001370503.1		c.673G>A	p.Glu225Lys	missense	Exon 8 of 8	NP_001357432.1	P78330
PSPH	NM_001370504.1		c.673G>A	p.Glu225Lys	missense	Exon 8 of 8	NP_001357433.1	P78330

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PSPH	ENST00000275605.8	TSL:1 MANE Select	c.673G>A	p.Glu225Lys	missense	Exon 8 of 8	ENSP00000275605.3	P78330
PSPH	ENST00000395471.7	TSL:1	c.673G>A	p.Glu225Lys	missense	Exon 8 of 8	ENSP00000378854.3	P78330
PSPH	ENST00000891724.1		c.673G>A	p.Glu225Lys	missense	Exon 8 of 8	ENSP00000561783.1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000111

AC:

AN:

251140

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000117

AC:

170

AN:

1457298

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

725290

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33346

American (AMR)

AF:

0.0000671

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39652

South Asian (SAS)

AF:

0.000116

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000136

AC:

151

AN:

1107902

Other (OTH)

AF:

0.0000498

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41520

American (AMR)

AF:

0.000131

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.548

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000184

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Deficiency of phosphoserine phosphatase (1)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0029

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.048

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.82

MutationAssessor

Benign

-1.6

PhyloP100

2.2

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.24

REVEL

Benign

0.24

Sift

Benign

0.45

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.19

MutPred

0.37

Gain of ubiquitination at E225 (P = 0.0177)

MVP

0.13

MPC

0.24

ClinPred

0.045

GERP RS

3.8

Varity_R

0.20

gMVP

0.76

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over