Genetic Variant PHOSPHO1:p.Gly17Arg (chr17-49225076-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001143804.2(PHOSPHO1):c.49G>C(p.Gly17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PHOSPHO1
NM_001143804.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24

Publications

1 publications found

Variant links:

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]

PHOSPHO1 links:

FLJ40194 (HGNC:):

FLJ40194 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035702527).

BP6

Variant 17-49225076-C-G is Benign according to our data. Variant chr17-49225076-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3417908.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143804.2. 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.46-72G>C		intron	N/A	NP_848595.1	Q8TCT1-1
	PHOSPHO1	NM_001143804.2		c.49G>C	p.Gly17Arg	missense	Exon 3 of 3	NP_001137276.1	Q8TCT1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PHOSPHO1	ENST00000514112.1	TSL:1	c.49G>C	p.Gly17Arg	missense	Exon 2 of 2	ENSP00000427694.1	Q8TCT1-3
PHOSPHO1	ENST00000310544.9	TSL:2 MANE Select	c.46-72G>C		intron	N/A	ENSP00000311925.4	Q8TCT1-1
PHOSPHO1	ENST00000574638.1	TSL:3	c.46-72G>C		intron	N/A	ENSP00000461392.1	I3L4N1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1292418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

627928

African (AFR)

AF:

0.00

AC:

AN:

28320

American (AMR)

AF:

0.00

AC:

AN:

20022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18958

East Asian (EAS)

AF:

0.00

AC:

AN:

35012

South Asian (SAS)

AF:

0.00

AC:

AN:

63522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5042

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1036734

Other (OTH)

AF:

0.00

AC:

AN:

53806

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.70

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.47

M_CAP

Benign

0.014

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.1

PhyloP100

1.2

PROVEAN

Benign

0.0

REVEL

Benign

0.050

Sift

Benign

0.90

Sift4G

Benign

0.79

Vest4

0.16

MutPred

0.15

Gain of methylation at G17 (P = 0.046)

MVP

0.043

ClinPred

0.045

GERP RS

2.1

gMVP

0.25

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over