10-132749597-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005539.5(INPP5A):c.813G>A(p.Ser271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,612,986 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0022 (8 hom.)
• Consequence: INPP5A NM_005539.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.45

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-132749597-G-A is Benign according to our data. Variant chr10-132749597-G-A is described in ClinVar as [Benign]. Clinvar id is 782211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP5A	NM_005539.5	c.813G>A	p.Ser271=	synonymous_variant	10/16	ENST00000368594.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP5A	ENST00000368594.8	c.813G>A	p.Ser271=	synonymous_variant	10/16	1	NM_005539.5	P1
INPP5A	ENST00000368593.7	c.813G>A	p.Ser271=	synonymous_variant	10/13	1
INPP5A	ENST00000342652.6	c.647-16176G>A		intron_variant		5
INPP5A	ENST00000498337.1	n.275G>A		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 276 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00300

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00196 AC: 491 AN: 250574 Hom.: 2 AF XY: 0.00222 AC XY: 302 AN XY: 135760

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00258

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00293

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00216 AC: 3152 AN: 1460626 Hom.: 8 Cov.: 31 AF XY: 0.00227 AC XY: 1649 AN XY: 726602

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00136

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00265

Gnomad4 FIN exome AF: 0.000421

Gnomad4 NFE exome AF: 0.00235

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152360 Hom.: 0 Cov.: 34 AF XY: 0.00180 AC XY: 134 AN XY: 74506

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00300

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00236 Hom.: 0

Bravo AF: 0.00184

Asia WGS AF: 0.00115 AC: 4 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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.80
Dann	Benign	0.83

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

Other links and lift over

dbSNP: rs143990293; hg19: chr10-134563101;