NM_004577.4:c.*317G>A

Variant names:

• chr7-56011445-C-T
• rs565399960
• NM_004577.4:c.*317G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004577.4(PSPH):​c.*317G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00034 in 182,384 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00079 (1 hom.)
• Consequence: PSPH NM_004577.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-56011445-C-T is Benign according to our data. Variant chr7-56011445-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 360499.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*317G>A		3_prime_UTR	Exon 8 of 8	NP_004568.2
	PSPH	NM_001370503.1		c.*317G>A		3_prime_UTR	Exon 8 of 8	NP_001357432.1	P78330
	PSPH	NM_001370504.1		c.*317G>A		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.*317G>A		3_prime_UTR	Exon 8 of 8	ENSP00000275605.3	P78330
	PSPH	ENST00000395471.7	TSL:1	c.*317G>A		3_prime_UTR	Exon 8 of 8	ENSP00000378854.3	P78330
	PSPH	ENST00000891724.1		c.*317G>A		3_prime_UTR	Exon 8 of 8	ENSP00000561783.1

Frequencies

GnomAD3 genomes AF: 0.000259 AC: 39 AN: 150490 Hom.: 1 Cov.: 28

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00454

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000192

Gnomad OTH AF: 0.000483

GnomAD4 exome AF: 0.000787 AC: 25 AN: 31778 Hom.: 1 Cov.: 0 AF XY: 0.00101 AC XY: 18 AN XY: 17896

African (AFR) AF: 0.00 AC: 0 AN: 656

American (AMR) AF: 0.000520 AC: 1 AN: 1924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 828

East Asian (EAS) AF: 0.00 AC: 0 AN: 1638

South Asian (SAS) AF: 0.00398 AC: 20 AN: 5030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.000208 AC: 4 AN: 19200

Other (OTH) AF: 0.00 AC: 0 AN: 1458

GnomAD4 genome AF: 0.000246 AC: 37 AN: 150606 Hom.: 0 Cov.: 28 AF XY: 0.000313 AC XY: 23 AN XY: 73532

African (AFR) AF: 0.0000243 AC: 1 AN: 41116

American (AMR) AF: 0.0000667 AC: 1 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 4970

South Asian (SAS) AF: 0.00433 AC: 20 AN: 4614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10352

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000192 AC: 13 AN: 67802

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000245 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of phosphoserine phosphatase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-0.95

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: rs565399960; hg19: chr7-56079138;