2-98539535-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001134225.2(INPP4A):c.678T>C(p.Gly226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 1,608,186 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (140 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (107 hom.)
• Consequence: INPP4A NM_001134225.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.56

Genes affected

INPP4A (HGNC:6074): (inositol polyphosphate-4-phosphatase type I A) This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 2-98539535-T-C is Benign according to our data. Variant chr2-98539535-T-C is described in ClinVar as [Benign]. Clinvar id is 783335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP4A	NM_001134225.2	c.678T>C	p.Gly226=	synonymous_variant	10/25	ENST00000409851.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP4A	ENST00000409851.8	c.678T>C	p.Gly226=	synonymous_variant	10/25	1	NM_001134225.2

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3376 AN: 152140 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00578 AC: 1420 AN: 245870 Hom.: 49 AF XY: 0.00439 AC XY: 586 AN XY: 133522

Gnomad AFR exome AF: 0.0817

Gnomad AMR exome AF: 0.00429

Gnomad ASJ exome AF: 0.000901

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000166

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.00203

GnomAD4 exome AF: 0.00228 AC: 3315 AN: 1455928 Hom.: 107 Cov.: 30 AF XY: 0.00196 AC XY: 1418 AN XY: 723574

Gnomad4 AFR exome AF: 0.0762

Gnomad4 AMR exome AF: 0.00498

Gnomad4 ASJ exome AF: 0.000806

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000257

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.00617

GnomAD4 genome AF: 0.0223 AC: 3395 AN: 152258 Hom.: 140 Cov.: 32 AF XY: 0.0219 AC XY: 1627 AN XY: 74448

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0109 Hom.: 19

Bravo AF: 0.0255

Asia WGS AF: 0.00837 AC: 29 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	-1.0
Cadd	Benign	0.022
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs35028575; hg19: chr2-99155998;