7-56011272-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004577.4(PSPH):c.*490C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0548 in 152,254 control chromosomes in the GnomAD database, including 299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (299 hom., cov: 31)
  • Exomes 𝑓: 0.048 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: PSPH NM_004577.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.391

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-56011272-G-A is Benign according to our data. Variant chr7-56011272-G-A is described in ClinVar as [Benign]. Clinvar id is 360494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSPH	NM_004577.4	c.*490C>T		3_prime_UTR_variant	8/8	ENST00000275605.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSPH	ENST00000275605.8	c.*490C>T		3_prime_UTR_variant	8/8	1	NM_004577.4	P1
PSPH	ENST00000395471.7	c.*490C>T		3_prime_UTR_variant	8/8	1		P1
PSPH	ENST00000437355.6	c.*219-39C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0549 AC: 8346 AN: 152136 Hom.: 298 Cov.: 31

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.0667

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0703

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0477 AC: 68 AN: 1426 Hom.: 2 Cov.: 0 AF XY: 0.0457 AC XY: 37 AN XY: 810

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0538

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0536

Gnomad4 FIN exome AF: 0.0478

Gnomad4 NFE exome AF: 0.0466

Gnomad4 OTH exome AF: 0.0789

GnomAD4 genome AF: 0.0548 AC: 8340 AN: 152254 Hom.: 299 Cov.: 31 AF XY: 0.0557 AC XY: 4144 AN XY: 74448

Gnomad4 AFR AF: 0.0126

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0667

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.0691

Alfa AF: 0.0626 Hom.: 51

Bravo AF: 0.0547

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of phosphoserine phosphatase Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.1
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs71543776; hg19: chr7-56078965;