7-56011401-T-C

Position:

• chr7-56011401-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004577.4(PSPH):​c.*361A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 159,234 control chromosomes in the GnomAD database, including 40,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38111 hom., cov: 27)
  • Exomes 𝑓: 0.70 (2024 hom.)
• Consequence: PSPH NM_004577.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.27

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 7-56011401-T-C is Benign according to our data. Variant chr7-56011401-T-C is described in ClinVar as [Benign]. Clinvar id is 360497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSPH	NM_004577.4	c.*361A>G		3_prime_UTR_variant	8/8	ENST00000275605.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSPH	ENST00000275605.8	c.*361A>G		3_prime_UTR_variant	8/8	1	NM_004577.4	P1
PSPH	ENST00000395471.7	c.*361A>G		3_prime_UTR_variant	8/8	1		P1
PSPH	ENST00000437355.6	c.*218+143A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.707 AC: 106775 AN: 151068 Hom.: 38084 Cov.: 27

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.703 AC: 5653 AN: 8046 Hom.: 2024 Cov.: 0 AF XY: 0.690 AC XY: 3216 AN XY: 4664

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.678

Gnomad4 ASJ exome AF: 0.642

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.828

Gnomad4 NFE exome AF: 0.737

Gnomad4 OTH exome AF: 0.676

GnomAD4 genome AF: 0.707 AC: 106855 AN: 151188 Hom.: 38111 Cov.: 27 AF XY: 0.710 AC XY: 52457 AN XY: 73834

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.695

Alfa AF: 0.676 Hom.: 1799

Bravo AF: 0.691

Asia WGS AF: 0.676 AC: 2351 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.15

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: rs4947534; hg19: chr7-56079094;