7-56011740-T-G

Variant names:

• chr7-56011740-T-G
• rs374366346
• NM_004577.4:c.*22A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004577.4(PSPH):​c.*22A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PSPH NM_004577.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.*22A>C		3_prime_UTR	Exon 8 of 8	NP_004568.2
	PSPH	NM_001370503.1		c.*22A>C		3_prime_UTR	Exon 8 of 8	NP_001357432.1	P78330
	PSPH	NM_001370504.1		c.*22A>C		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.*22A>C		3_prime_UTR	Exon 8 of 8	ENSP00000275605.3	P78330
	PSPH	ENST00000395471.7	TSL:1	c.*22A>C		3_prime_UTR	Exon 8 of 8	ENSP00000378854.3	P78330
	PSPH	ENST00000891765.1		c.*22A>C		splice_region	Exon 9 of 9	ENSP00000561824.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.35
PhyloP100		-0.35

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: rs374366346; hg19: chr7-56079433;