chr17-49224932-C-G

Position:

• chr17-49224932-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178500.4(PHOSPHO1):​c.118G>C​(p.Glu40Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHOSPHO1 NM_178500.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70

Genes affected

PHOSPHO1 (HGNC:16815): (phosphoethanolamine/phosphocholine phosphatase 1) Enables pyrophosphatase activity. Predicted to be involved in bone mineralization involved in bone maturation. Predicted to act upstream of or within endochondral ossification. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHOSPHO1	NM_178500.4	c.118G>C	p.Glu40Gln	missense_variant	3/3	ENST00000310544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHOSPHO1	ENST00000310544.9	c.118G>C	p.Glu40Gln	missense_variant	3/3	2	NM_178500.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2023

The c.193G>C (p.E65Q) alteration is located in exon 3 (coding exon 1) of the PHOSPHO1 gene. This alteration results from a G to C substitution at nucleotide position 193, causing the glutamic acid (E) at amino acid position 65 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;.;.;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;D;.;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.1	N;N;N;N;.;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.020	D;D;D;D;.;D;D
Sift4G	Uncertain	0.014	D;D;D;.;.;.;.
Polyphen		1.0	D;.;.;.;.;.;.
Vest4		0.47
MutPred		0.40		Loss of phosphorylation at S42 (P = 0.1194);.;.;Loss of phosphorylation at S42 (P = 0.1194);Loss of phosphorylation at S42 (P = 0.1194);.;.;
MVP		0.12
ClinPred		0.92	D
GERP RS		4.5
Varity_R		0.33
gMVP		0.70

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: rs879666747; hg19: chr17-47302294;