chr4-142145942-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101669.3. 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
	INPP4B	NM_001101669.3	MANE Select	c.1618G>A	p.Asp540Asn	missense	Exon 18 of 26	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.1618G>A	p.Asp540Asn	missense	Exon 18 of 26	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.1618G>A	p.Asp540Asn	missense	Exon 17 of 25	NP_001372264.1	E7EQN9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4B	ENST00000262992.9	TSL:5 MANE Select	c.1618G>A	p.Asp540Asn	missense	Exon 18 of 26	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.1618G>A	p.Asp540Asn	missense	Exon 17 of 25	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.1618G>A	p.Asp540Asn	missense	Exon 19 of 27	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.014	D
Polyphen		0.98	D
Vest4		0.63
MutPred		0.58		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
Mutation Taster		=75/25	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

hg19: chr4-143067095;