2-98543988-C-T

Variant summary

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

The NM_001134225.2(INPP4A):c.930C>T(p.Thr310=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,566,614 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00072 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (9 hom.)
• Consequence: INPP4A NM_001134225.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 2-98543988-C-T is Benign according to our data. Variant chr2-98543988-C-T is described in ClinVar as [Benign]. Clinvar id is 719167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP4A	NM_001134225.2	c.930C>T	p.Thr310=	synonymous_variant	11/25	ENST00000409851.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP4A	ENST00000409851.8	c.930C>T	p.Thr310=	synonymous_variant	11/25	1	NM_001134225.2

Frequencies

GnomAD3 genomes AF: 0.000717 AC: 109 AN: 152098 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00155 AC: 268 AN: 172736 Hom.: 3 AF XY: 0.00159 AC XY: 146 AN XY: 91598

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000961

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0103

Gnomad SAS exome AF: 0.00471

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000569

Gnomad OTH exome AF: 0.000632

GnomAD4 exome AF: 0.000720 AC: 1018 AN: 1414398 Hom.: 9 Cov.: 32 AF XY: 0.000812 AC XY: 568 AN XY: 699130

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000883

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0152

Gnomad4 SAS exome AF: 0.00433

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000230

Gnomad4 OTH exome AF: 0.000799

GnomAD4 genome AF: 0.000716 AC: 109 AN: 152216 Hom.: 2 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74426

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0101

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.000495

Asia WGS AF: 0.00664 AC: 23 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	-0.47
Cadd	Benign	2.6
Dann	Benign	0.79

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: rs74531966; hg19: chr2-99160451;