ENST00000514112.1:c.49G>A

Variant names:

• chr17-49225076-C-T
• rs766758664
• ENST00000514112.1:c.49G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000514112.1(PHOSPHO1):​c.49G>A​(p.Gly17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000774 in 1,292,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: PHOSPHO1 ENST00000514112.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 1 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHOSPHO1	NM_178500.4	c.46-72G>A		intron_variant	Intron 2 of 2	ENST00000310544.9	NP_848595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHOSPHO1	ENST00000310544.9	c.46-72G>A		intron_variant	Intron 2 of 2	2	NM_178500.4	ENSP00000311925.4
PHOSPHO1	ENST00000574638.1	c.46-72G>A		intron_variant	Intron 2 of 2	3		ENSP00000461392.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.74e-7 AC: 1 AN: 1292420 Hom.: 0 Cov.: 31 AF XY: 0.00000159 AC XY: 1 AN XY: 627930

African (AFR) AF: 0.00 AC: 0 AN: 28320

American (AMR) AF: 0.00 AC: 0 AN: 20022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18958

East Asian (EAS) AF: 0.00 AC: 0 AN: 35012

South Asian (SAS) AF: 0.00 AC: 0 AN: 63522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5042

European-Non Finnish (NFE) AF: 9.65e-7 AC: 1 AN: 1036736

Other (OTH) AF: 0.00 AC: 0 AN: 53806

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.87
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.47	T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.047	T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		1.2
PROVEAN	Benign	0.0	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.90	T;T;T;T
Sift4G	Benign	0.79	T;T;.;.
Vest4		0.16
MutPred		0.15		Gain of methylation at G17 (P = 0.046);Gain of methylation at G17 (P = 0.046);Gain of methylation at G17 (P = 0.046);.;
MVP		0.043
ClinPred		0.059	T
GERP RS		2.1
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766758664; hg19: chr17-47302438;