4-142145852-A-G

Variant names:

• chr4-142145852-A-G
• NM_001101669.3:c.1708T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001101669.3(INPP4B):​c.1708T>C​(p.Ser570Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: INPP4B NM_001101669.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089838356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4B	NM_001101669.3	c.1708T>C	p.Ser570Pro	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.1708T>C	p.Ser570Pro	missense_variant	Exon 18 of 26	5	NM_001101669.3	ENSP00000262992.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461406 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.0
DANN	Benign	0.94
DEOGEN2	Benign	0.18	T;T;T;T;T;.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.58	.;T;.;T;T;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.090	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L;.;.;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.5	D;D;D;D;N;N;N
REVEL	Benign	0.033
Sift	Benign	0.16	T;T;T;T;T;T;T
Sift4G	Benign	0.19	T;T;T;T;.;.;T
Polyphen		0.30	B;B;B;.;.;.;.
Vest4		0.065
MutPred		0.32		Gain of catalytic residue at P569 (P = 0.012);Gain of catalytic residue at P569 (P = 0.012);Gain of catalytic residue at P569 (P = 0.012);Gain of catalytic residue at P569 (P = 0.012);.;Gain of catalytic residue at P569 (P = 0.012);.;
MVP		0.16
MPC		0.24
ClinPred		0.11	T
GERP RS		-3.8
Varity_R		0.17
gMVP		0.32

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: chr4-143067005;