7-56011528-C-CA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004577.4(PSPH):c.*233_*234insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.24 (3542 hom., cov: 0)
  • Exomes 𝑓: 0.22 (98 hom.)
• Consequence: PSPH NM_004577.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.568

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSPH	NM_004577.4	c.*233_*234insT		3_prime_UTR_variant	8/8	ENST00000275605.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSPH	ENST00000275605.8	c.*233_*234insT		3_prime_UTR_variant	8/8	1	NM_004577.4	P1
PSPH	ENST00000395471.7	c.*233_*234insT		3_prime_UTR_variant	8/8	1		P1
PSPH	ENST00000437355.6	c.*218+15_*218+16insT		intron_variant, NMD_transcript_variant		5
PSPH	ENST00000459834.5			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.244 AC: 30097 AN: 123304 Hom.: 3546 Cov.: 0

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.216 AC: 21857 AN: 100970 Hom.: 98 Cov.: 0 AF XY: 0.221 AC XY: 12433 AN XY: 56166

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.271

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.244 AC: 30084 AN: 123344 Hom.: 3542 Cov.: 0 AF XY: 0.248 AC XY: 14624 AN XY: 58994

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.280

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of phosphoserine phosphatase Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs34727399; hg19: chr7-56079221;