8-91020173-A-T

Position:

• chr8-91020173-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000285419.8(PIP4P2):​c.346T>A​(p.Cys116Ser) 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: 32)
• Consequence: PIP4P2 ENST00000285419.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

Genes affected

PIP4P2 (HGNC:25452): (phosphatidylinositol-4,5-bisphosphate 4-phosphatase 2) TMEM55A 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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIP4P2	NM_018710.3	c.346T>A	p.Cys116Ser	missense_variant	3/7	ENST00000285419.8	NP_061180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIP4P2	ENST00000285419.8	c.346T>A	p.Cys116Ser	missense_variant	3/7	1	NM_018710.3	ENSP00000285419.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.346T>A (p.C116S) alteration is located in exon 3 (coding exon 3) of the TMEM55A gene. This alteration results from a T to A substitution at nucleotide position 346, causing the cysteine (C) at amino acid position 116 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.93	D;D
MetaSVM	Uncertain	-0.16	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-9.5	D;D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.97	D;.
Vest4		0.94
MutPred		0.80		Gain of phosphorylation at C116 (P = 0.0157);.;
MVP		0.77
MPC		1.1
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.95
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-92032401;