7-56011401-T-C

Variant names:

• chr7-56011401-T-C
• rs4947534
• NM_004577.4:c.*361A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSPH	NM_004577.4	MANE Select	c.*361A>G		3_prime_UTR	Exon 8 of 8	NP_004568.2
	PSPH	NM_001370503.1		c.*361A>G		3_prime_UTR	Exon 8 of 8	NP_001357432.1	P78330
	PSPH	NM_001370504.1		c.*361A>G		3_prime_UTR	Exon 8 of 8	NP_001357433.1	P78330

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSPH	ENST00000275605.8	TSL:1 MANE Select	c.*361A>G		3_prime_UTR	Exon 8 of 8	ENSP00000275605.3	P78330
	PSPH	ENST00000395471.7	TSL:1	c.*361A>G		3_prime_UTR	Exon 8 of 8	ENSP00000378854.3	P78330
	PSPH	ENST00000891724.1		c.*361A>G		3_prime_UTR	Exon 8 of 8	ENSP00000561783.1

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

African (AFR) AF: 0.622 AC: 92 AN: 148

American (AMR) AF: 0.678 AC: 491 AN: 724

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 86 AN: 134

East Asian (EAS) AF: 0.655 AC: 220 AN: 336

South Asian (SAS) AF: 0.586 AC: 681 AN: 1162

European-Finnish (FIN) AF: 0.828 AC: 144 AN: 174

Middle Eastern (MID) AF: 0.692 AC: 18 AN: 26

European-Non Finnish (NFE) AF: 0.737 AC: 3714 AN: 5036

Other (OTH) AF: 0.676 AC: 207 AN: 306

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

African (AFR) AF: 0.614 AC: 25240 AN: 41104

American (AMR) AF: 0.697 AC: 10562 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2276 AN: 3464

East Asian (EAS) AF: 0.707 AC: 3608 AN: 5102

South Asian (SAS) AF: 0.637 AC: 3050 AN: 4786

European-Finnish (FIN) AF: 0.814 AC: 8527 AN: 10478

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51293 AN: 67808

Other (OTH) AF: 0.695 AC: 1462 AN: 2104

Alfa AF: 0.676 Hom.: 1799

Bravo AF: 0.691

Asia WGS AF: 0.676 AC: 2351 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of phosphoserine phosphatase (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.15
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4947534; hg19: chr7-56079094;