4-142108117-A-C

Variant names:

• chr4-142108117-A-C
• NM_001101669.3:c.2350T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001101669.3(INPP4B):​c.2350T>G​(p.Phe784Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: INPP4B NM_001101669.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

Genes affected

INPP4B (HGNC:6075): (inositol polyphosphate-4-phosphatase type II B) INPP4B encodes the inositol polyphosphate 4-phosphatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. There is limited data to suggest that the human type II enzyme is subject to alternative splicing, as has been established for the type I enzyme. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
INPP4B	NM_001101669.3	c.2350T>G	p.Phe784Val	missense_variant	Exon 23 of 26	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.2350T>G	p.Phe784Val	missense_variant	Exon 23 of 26	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2350T>G (p.F784V) alteration is located in exon 24 (coding exon 20) of the INPP4B gene. This alteration results from a T to G substitution at nucleotide position 2350, causing the phenylalanine (F) at amino acid position 784 to be replaced by a valine (V). 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	Benign	0.15
BayesDel_addAF	Benign	0.0048	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D;D;D;T;T;.;T
Eigen	Benign	0.0054
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	.;D;.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;L;.;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.3	D;D;D;D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D;D;D;D;D;T;T
Sift4G	Uncertain	0.011	D;D;D;D;.;.;D
Polyphen		0.0040	B;B;B;.;.;.;.
Vest4		0.63
MutPred		0.65		Gain of catalytic residue at F784 (P = 0.0208);Gain of catalytic residue at F784 (P = 0.0208);Gain of catalytic residue at F784 (P = 0.0208);Gain of catalytic residue at F784 (P = 0.0208);.;Gain of catalytic residue at F784 (P = 0.0208);.;
MVP		0.46
MPC		0.27
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.31
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr4-143029270;