Genetic Variant INPP5A:p.Leu237Leu (chr10-132726884-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005539.5(INPP5A):c.711G>A(p.Leu237Leu) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,609,452 control chromosomes in the GnomAD database, including 258 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 132 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 126 hom. )

Consequence

INPP5A
NM_005539.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.34

Publications

2 publications found

Variant links:

Genes affected

INPP5A (HGNC:6076): (inositol polyphosphate-5-phosphatase A) The protein encoded by this gene is a membrane-associated type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. [provided by RefSeq, Jul 2008]

INPP5A links:

ENSG00000293889 (HGNC:):

ENSG00000293889 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 10-132726884-G-A is Benign according to our data. Variant chr10-132726884-G-A is described in ClinVar as [Benign]. Clinvar id is 769791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP5A	NM_005539.5 link	c.711G>A	p.Leu237Leu	synonymous_variant	Exon 9 of 16	ENST00000368594.8	NP_005530.3	Q14642

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP5A	ENST00000368594.8 link	c.711G>A	p.Leu237Leu	synonymous_variant	Exon 9 of 16	1	NM_005539.5	ENSP00000357583.3		Q14642

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3593

AN:

152120

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0810

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0100

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.00635

AC:

1589

AN:

250408

AF XY:

0.00473

show subpopulations

Gnomad AFR exome

AF:

0.0800

Gnomad AMR exome

AF:

0.00552

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000520

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.00264

AC:

3842

AN:

1457214

Hom.:

126

Cov.:

AF XY:

0.00226

AC XY:

1639

AN XY:

724570

show subpopulations

African (AFR)

AF:

0.0802

AC:

2676

AN:

33356

American (AMR)

AF:

0.00635

AC:

282

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.000307

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39506

South Asian (SAS)

AF:

0.000232

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00504

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000383

AC:

425

AN:

1108584

Other (OTH)

AF:

0.00668

AC:

402

AN:

60178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

168

336

503

671

839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0237

AC:

3614

AN:

152238

Hom.:

132

Cov.:

AF XY:

0.0229

AC XY:

1705

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0812

AC:

3372

AN:

41506

American (AMR)

AF:

0.0100

AC:

153

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000676

AC:

AN:

68016

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

173

346

519

692

865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0122

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.00549

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

Jun 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

7.3

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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chr10-132726884-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over