17-49225115-G-T

Variant names:

• chr17-49225115-G-T
• rs1277427387
• ENST00000514112.1:c.10C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178500.4(PHOSPHO1):​c.46-111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000776 in 1,289,000 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: PHOSPHO1 NM_178500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080034345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHOSPHO1	NM_178500.4	c.46-111C>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.46-111C>A		intron_variant	Intron 2 of 2	2	NM_178500.4	ENSP00000311925.4
PHOSPHO1	ENST00000574638.1	c.46-111C>A		intron_variant	Intron 2 of 2	3		ENSP00000461392.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.76e-7 AC: 1 AN: 1289000 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 625770

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28256

American (AMR) AF: 0.00 AC: 0 AN: 19696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18886

East Asian (EAS) AF: 0.00 AC: 0 AN: 34932

South Asian (SAS) AF: 0.00 AC: 0 AN: 63106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4692

European-Non Finnish (NFE) AF: 9.66e-7 AC: 1 AN: 1035310

Other (OTH) AF: 0.00 AC: 0 AN: 53648

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.97
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.45	T;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.1
PROVEAN	Benign	-0.26	N;N;N;N
REVEL	Benign	0.034
Sift	Uncertain	0.016	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;.;.
Vest4		0.33
MutPred		0.22		Loss of MoRF binding (P = 0.0024);Loss of MoRF binding (P = 0.0024);Loss of MoRF binding (P = 0.0024);.;
MVP		0.043
ClinPred		0.16	T
GERP RS		3.1
gMVP		0.45

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: rs1277427387; hg19: chr17-47302477;