4-142124619-G-C

Variant names:

• chr4-142124619-G-C
• rs145209328
• NM_001101669.3:c.1862C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001101669.3(INPP4B):​c.1862C>G​(p.Thr621Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T621M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INPP4B NM_001101669.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.67
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4184143).

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.1862C>G	p.Thr621Arg	missense	Exon 19 of 26	NP_001095139.1	O15327-1
	INPP4B	NM_001331040.1		c.1862C>G	p.Thr621Arg	missense	Exon 19 of 26	NP_001317969.1	O15327
	INPP4B	NM_001385335.1		c.1862C>G	p.Thr621Arg	missense	Exon 18 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.1862C>G	p.Thr621Arg	missense	Exon 19 of 26	ENSP00000262992.4	O15327-1
	INPP4B	ENST00000508116.5	TSL:1	c.1862C>G	p.Thr621Arg	missense	Exon 18 of 25	ENSP00000423954.1	O15327-1
	INPP4B	ENST00000513000.5	TSL:1	c.1862C>G	p.Thr621Arg	missense	Exon 20 of 27	ENSP00000425487.1	O15327-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.26
Sift	Benign	0.51	T
Sift4G	Benign	0.26	T
Polyphen		0.98	D
Vest4		0.81
MutPred		0.51		Loss of catalytic residue at T621 (P = 0.1646)
MVP		0.22
MPC		0.71
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.15
gMVP		0.53
Mutation Taster		=82/18	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: rs145209328; hg19: chr4-143045772;