rs372999773

Variant names:

• chr14-20461232-C-A
• rs372999773
• NM_144568.4:c.94G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-20461232-C-A
• chr14-20461232-C-T

Variant summary

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

The NM_144568.4(PIP4P1):​c.94G>T​(p.Ala32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000902 in 1,108,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A32T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: PIP4P1 NM_144568.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957
• Publications: 0 publications found

Genes affected

PIP4P1 (HGNC:19299): (phosphatidylinositol-4,5-bisphosphate 4-phosphatase 1) TMEM55B catalyzes the degradation of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2) by removing the 4-phosphate (Ungewickell et al., 2005 [PubMed 16365287]).[supplied by OMIM, Mar 2008]

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=0.21423101).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144568.4. 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
	PIP4P1	NM_144568.4	MANE Select	c.94G>T	p.Ala32Ser	missense	Exon 1 of 7	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.94G>T	p.Ala32Ser	missense	Exon 1 of 7	NP_001094284.1	Q86T03-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4P1	ENST00000250489.9	TSL:1 MANE Select	c.94G>T	p.Ala32Ser	missense	Exon 1 of 7	ENSP00000250489.4	Q86T03-1
	PIP4P1	ENST00000398020.6	TSL:1	c.94G>T	p.Ala32Ser	missense	Exon 1 of 7	ENSP00000381102.4	Q86T03-2
	PIP4P1	ENST00000924695.1		c.94G>T	p.Ala32Ser	missense	Exon 1 of 7	ENSP00000594754.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.02e-7 AC: 1 AN: 1108818 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 525842

⚠️ 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: 23572

American (AMR) AF: 0.00 AC: 0 AN: 10636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14552

East Asian (EAS) AF: 0.00 AC: 0 AN: 27422

South Asian (SAS) AF: 0.00 AC: 0 AN: 21632

European-Finnish (FIN) AF: 0.0000309 AC: 1 AN: 32370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 930068

Other (OTH) AF: 0.00 AC: 0 AN: 44458

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.96
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.24
Sift	Benign	0.38	T
Sift4G	Benign	0.83	T
Polyphen		0.98	D
Vest4		0.15
MutPred		0.41		Gain of catalytic residue at S30 (P = 0)
MVP		0.068
MPC		0.52
ClinPred		0.60	D
GERP RS		3.6
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.043
gMVP		0.17
Mutation Taster		=93/7	polymorphism

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: rs372999773; hg19: chr14-20929391;