Variant 17-1496364-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016532.4(INPP5K):c.1140C>T(p.Ala380Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,565,008 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 12 hom. )

Consequence

INPP5K
NM_016532.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.771

Variant links:

Genes affected

INPP5K (HGNC:33882): (inositol polyphosphate-5-phosphatase K) This gene encodes a protein with 5-phosphatase activity toward polyphosphate inositol. The protein localizes to the cytosol in regions lacking actin stress fibers. It is thought that this protein may negatively regulate the actin cytoskeleton. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

INPP5K links:

INPP5K (HGNC:):

INPP5K links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-1496364-G-A is Benign according to our data. Variant chr17-1496364-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.771 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00211 (321/152322) while in subpopulation NFE AF= 0.00297 (202/68026). AF 95% confidence interval is 0.00263. There are 0 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP5K	NM_016532.4 linkuse as main transcript	c.1140C>T	p.Ala380Ala	synonymous_variant	10/12	ENST00000421807.7	NP_057616.2	Q9BT40-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP5K	ENST00000421807.7 linkuse as main transcript	c.1140C>T	p.Ala380Ala	synonymous_variant	10/12	1	NM_016532.4	ENSP00000413937.2		Q9BT40-1

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00183

AC:

323

AN:

176080

Hom.:

AF XY:

0.00162

AC XY:

151

AN XY:

93236

show subpopulations

Gnomad AFR exome

AF:

0.000849

Gnomad AMR exome

AF:

0.00218

Gnomad ASJ exome

AF:

0.00160

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00303

Gnomad OTH exome

AF:

0.00337

GnomAD4 exome

AF:

0.00260

AC:

3668

AN:

1412686

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1765

AN XY:

697970

show subpopulations

Gnomad4 AFR exome

AF:

0.000369

Gnomad4 AMR exome

AF:

0.00243

Gnomad4 ASJ exome

AF:

0.00210

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000149

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.00305

Gnomad4 OTH exome

AF:

0.00256

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152322

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

147

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00297

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.00246

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	INPP5K: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over