Genetic Variant INPP5B:p.Ala51Asp (chr1-37945756-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001365825.1(INPP5B):c.-108C>A variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000685 in 1,460,328 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

INPP5B
NM_001365825.1 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.9488

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.92

Publications

0 publications found

Variant links:

Genes affected

INPP5B (HGNC:6077): (inositol polyphosphate-5-phosphatase B) This gene encodes a member of a family of inositol polyphosphate-5-phosphatases. These enzymes function in the regulation of calcium signaling by inactivating inositol phosphates. The encoded protein is localized to the cytosol and mitochondria, and associates with membranes through an isoprenyl modification near the C-terminus. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2014]

INPP5B links:

LOC105378651 (HGNC:):

LOC105378651 links:

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new If you want to explore the variant's impact on the transcript NM_001365825.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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_001365825.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INPP5B	NM_005540.3	MANE Select	c.152C>A	p.Ala51Asp	missense splice_region	Exon 3 of 24	NP_005531.2	P32019-2
INPP5B	NM_001365825.1		c.-108C>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 23	NP_001352754.1
INPP5B	NM_001365820.1		c.152C>A	p.Ala51Asp	missense splice_region	Exon 3 of 24	NP_001352749.1	P32019-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INPP5B	ENST00000373024.8	TSL:1 MANE Select	c.152C>A	p.Ala51Asp	missense splice_region	Exon 3 of 24	ENSP00000362115.3	P32019-2
INPP5B	ENST00000373026.5	TSL:5	c.152C>A	p.Ala51Asp	missense splice_region	Exon 2 of 23	ENSP00000362117.1	P32019-1
INPP5B	ENST00000373021.1	TSL:1	c.152C>A	p.Ala51Asp	missense splice_region	Exon 2 of 6	ENSP00000362112.1	B1ARF3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460328

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726538

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110842

Other (OTH)

AF:

0.00

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.59

MetaSVM

Pathogenic

0.81

PhyloP100

3.9

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

Sift4G

Benign

0.073

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.85

Mutation Taster

=54/46

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Pathogenic

0.83

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over