10-132726884-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_005539.5(INPP5A):c.711G>A(p.Leu237=) 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. In-silico tool predicts a benign outcome for this variant. 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.34

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• 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_single_submitter, 1 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/exons	MANE	UniProt
INPP5A	NM_005539.5	c.711G>A	p.Leu237=	synonymous_variant	9/16	ENST00000368594.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP5A	ENST00000368594.8	c.711G>A	p.Leu237=	synonymous_variant	9/16	1	NM_005539.5	P1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3593 AN: 152120 Hom.: 131 Cov.: 33

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

GnomAD3 exomes AF: 0.00635 AC: 1589 AN: 250408 Hom.: 51 AF XY: 0.00473 AC XY: 641 AN XY: 135386

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 SAS exome AF: 0.000230

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.: 29 AF XY: 0.00226 AC XY: 1639 AN XY: 724570

Gnomad4 AFR exome AF: 0.0802

Gnomad4 AMR exome AF: 0.00635

Gnomad4 ASJ exome AF: 0.000307

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000383

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.0237 AC: 3614 AN: 152238 Hom.: 132 Cov.: 33 AF XY: 0.0229 AC XY: 1705 AN XY: 74456

Gnomad4 AFR AF: 0.0812

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0112 Hom.: 36

Bravo AF: 0.0269

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	12
Dann	Benign	0.79

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

Other links and lift over

dbSNP: rs34902202; hg19: chr10-134540388;