Variant chr7-56011751-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004577.4(PSPH):c.*11C>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 0.0687 in 1,593,728 control chromosomes in the GnomAD database, including 4,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 300 hom., cov: 31)

Exomes 𝑓: 0.070 ( 3707 hom. )

Consequence

PSPH
NM_004577.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.515

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 7-56011751-G-A is Benign according to our data. Variant chr7-56011751-G-A is described in ClinVar as [Benign]. Clinvar id is 360504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSPH	NM_004577.4 linkuse as main transcript	c.*11C>T		3_prime_UTR_variant	8/8	ENST00000275605.8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
PSPH	ENST00000275605.8 linkuse as main transcript	c.*11C>T	3_prime_UTR_variant	8/8	1	NM_004577.4	P1
PSPH	ENST00000395471.7 linkuse as main transcript	c.*11C>T	3_prime_UTR_variant	8/8	1		P1
PSPH	ENST00000459834.5 linkuse as main transcript	n.479C>T	non_coding_transcript_exon_variant	3/3	3
PSPH	ENST00000437355.6 linkuse as main transcript	c.*11C>T	3_prime_UTR_variant, NMD_transcript_variant	6/7	5

Frequencies

GnomAD3 genomes

AF:

0.0550

AC:

8356

AN:

151952

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0125

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0787

Gnomad ASJ

AF:

0.0646

Gnomad EAS

AF:

0.0307

Gnomad SAS

AF:

0.0671

Gnomad FIN

AF:

0.0666

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0740

Gnomad OTH

AF:

0.0703

GnomAD3 exomes

AF:

0.0709

AC:

17796

AN:

251098

Hom.:

716

AF XY:

0.0708

AC XY:

9611

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.0124

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.0705

Gnomad EAS exome

AF:

0.0365

Gnomad SAS exome

AF:

0.0738

Gnomad FIN exome

AF:

0.0661

Gnomad NFE exome

AF:

0.0709

Gnomad OTH exome

AF:

0.0723

GnomAD4 exome

AF:

0.0702

AC:

101176

AN:

1441658

Hom.:

3707

Cov.:

AF XY:

0.0703

AC XY:

50524

AN XY:

718618

show subpopulations

Gnomad4 AFR exome

AF:

0.0110

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.0732

Gnomad4 EAS exome

AF:

0.0460

Gnomad4 SAS exome

AF:

0.0691

Gnomad4 FIN exome

AF:

0.0653

Gnomad4 NFE exome

AF:

0.0718

Gnomad4 OTH exome

AF:

0.0647

GnomAD4 genome

AF:

0.0549

AC:

8350

AN:

152070

Hom.:

300

Cov.:

AF XY:

0.0559

AC XY:

4154

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0125

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.0646

Gnomad4 EAS

AF:

0.0306

Gnomad4 SAS

AF:

0.0670

Gnomad4 FIN

AF:

0.0666

Gnomad4 NFE

AF:

0.0740

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0674

Hom.:

101

Bravo

AF:

0.0547

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of phosphoserine phosphatase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

-0.92

CADD

Benign

0.20

DANN

Benign

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over