4-142145942-C-T

Variant names:

• chr4-142145942-C-T
• NM_001101669.3:c.1618G>A

Variant summary

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

The NM_001101669.3(INPP4B):​c.1618G>A​(p.Asp540Asn) 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: 5.75

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.1618G>A	p.Asp540Asn	missense_variant	Exon 18 of 26	ENST00000262992.9	NP_001095139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4B	ENST00000262992.9	c.1618G>A	p.Asp540Asn	missense_variant	Exon 18 of 26	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1618G>A (p.D540N) alteration is located in exon 19 (coding exon 15) of the INPP4B gene. This alteration results from a G to A substitution at nucleotide position 1618, causing the aspartic acid (D) at amino acid position 540 to be replaced by an asparagine (N). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	T;T;T;T;T;.;T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	.;D;.;D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.7	M;M;M;.;.;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0090	D;D;D;D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D;.;.;D
Polyphen		0.98	D;D;D;.;.;.;.
Vest4		0.63
MutPred		0.58		Gain of MoRF binding (P = 0.0388);Gain of MoRF binding (P = 0.0388);Gain of MoRF binding (P = 0.0388);Gain of MoRF binding (P = 0.0388);.;Gain of MoRF binding (P = 0.0388);.;
MVP		0.48
MPC		0.74
ClinPred		0.98	D
GERP RS		6.1
Varity_R		0.40
gMVP		0.60

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-143067095;