chr17-49224748-C-T

Variant names:

• chr17-49224748-C-T
• rs1363823988
• NM_178500.4:c.302G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_178500.4(PHOSPHO1):​c.302G>A​(p.Gly101Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHOSPHO1 NM_178500.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44
• Publications: 0 publications found

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]

FLJ40194 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178500.4. 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
	PHOSPHO1	NM_178500.4	MANE Select	c.302G>A	p.Gly101Asp	missense	Exon 3 of 3	NP_848595.1	Q8TCT1-1
	PHOSPHO1	NM_001143804.2		c.377G>A	p.Gly126Asp	missense	Exon 3 of 3	NP_001137276.1	Q8TCT1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHOSPHO1	ENST00000310544.9	TSL:2 MANE Select	c.302G>A	p.Gly101Asp	missense	Exon 3 of 3	ENSP00000311925.4	Q8TCT1-1
	PHOSPHO1	ENST00000514112.1	TSL:1	c.377G>A	p.Gly126Asp	missense	Exon 2 of 2	ENSP00000427694.1	Q8TCT1-3
	PHOSPHO1	ENST00000413580.5	TSL:2	c.377G>A	p.Gly126Asp	missense	Exon 3 of 3	ENSP00000406909.1	Q8TCT1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 222518 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447004 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718640

African (AFR) AF: 0.00 AC: 0 AN: 33154

American (AMR) AF: 0.00 AC: 0 AN: 42394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 38794

South Asian (SAS) AF: 0.00 AC: 0 AN: 84116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105252

Other (OTH) AF: 0.00 AC: 0 AN: 59806

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.76		Loss of catalytic residue at G101 (P = 0.0892)
MVP		0.30
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.77
gMVP		0.98

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: rs1363823988; hg19: chr17-47302110;