Variant 17-1496328-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.1176C>T(p.Asn392Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,561,010 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00062 ( 12 hom. )

Consequence

INPP5K
NM_016532.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.39

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 17-1496328-G-A is Benign according to our data. Variant chr17-1496328-G-A is described in ClinVar as [Benign]. Clinvar id is 778651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00601 (915/152342) while in subpopulation AFR AF= 0.0209 (868/41580). AF 95% confidence interval is 0.0197. There are 7 homozygotes in gnomad4. There are 433 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP5K	NM_016532.4 linkuse as main transcript	c.1176C>T	p.Asn392Asn	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.1176C>T	p.Asn392Asn	synonymous_variant	10/12	1	NM_016532.4	ENSP00000413937.2		Q9BT40-1

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

909

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00152

AC:

260

AN:

170890

Hom.:

AF XY:

0.00106

AC XY:

AN XY:

90384

show subpopulations

Gnomad AFR exome

AF:

0.0218

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000421

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000144

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.000623

AC:

878

AN:

1408668

Hom.:

Cov.:

AF XY:

0.000533

AC XY:

371

AN XY:

695722

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000499

Gnomad4 FIN exome

AF:

0.0000200

Gnomad4 NFE exome

AF:

0.0000332

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00601

AC:

915

AN:

152342

Hom.:

Cov.:

AF XY:

0.00581

AC XY:

433

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0209

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00682

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.79

CADD

Benign

4.3

DANN

Benign

0.71

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

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