rs2281983

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005029.4(PITX3):c.285C>T(p.Ile95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,608,126 control chromosomes in the GnomAD database, including 315,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32878 hom., cov: 32)

Exomes 𝑓: 0.62 ( 282782 hom. )

Consequence

PITX3
NM_005029.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.215

Variant links:

Genes affected

PITX3 (HGNC:9006): (paired like homeodomain 3) This gene encodes a member of the RIEG/PITX homeobox family, which is in the bicoid class of homeodomain proteins. Members of this family act as transcription factors. This protein is involved in lens formation during eye development. Mutations of this gene have been associated with anterior segment mesenchymal dysgenesis and congenital cataracts. [provided by RefSeq, Jul 2008]

PITX3 links:

GBF1 (HGNC:):

GBF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 10-102231624-G-A is Benign according to our data. Variant chr10-102231624-G-A is described in ClinVar as [Benign]. Clinvar id is 196404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-102231624-G-A is described in Lovd as [Benign]. Variant chr10-102231624-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.215 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PITX3	NM_005029.4 linkuse as main transcript	c.285C>T	p.Ile95=	synonymous_variant	3/4	ENST00000370002.8	NP_005020.1
PITX3	XM_047425352.1 linkuse as main transcript	c.285C>T	p.Ile95=	synonymous_variant	2/3		XP_047281308.1
GBF1	NM_001391923.1 linkuse as main transcript	c.-11+708G>A		intron_variant			NP_001378852.1
GBF1	NM_001391924.1 linkuse as main transcript	c.-149+708G>A		intron_variant			NP_001378853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITX3	ENST00000370002.8 linkuse as main transcript	c.285C>T	p.Ile95=	synonymous_variant	3/4	1	NM_005029.4	ENSP00000359019	P1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99367

AN:

151924

Hom.:

32833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.750

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.611

Gnomad ASJ

AF:

0.589

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.627

GnomAD3 exomes

AF:

0.617

AC:

148912

AN:

241510

Hom.:

46390

AF XY:

0.609

AC XY:

79867

AN XY:

131074

show subpopulations

Gnomad AFR exome

AF:

0.749

Gnomad AMR exome

AF:

0.581

Gnomad ASJ exome

AF:

0.571

Gnomad EAS exome

AF:

0.772

Gnomad SAS exome

AF:

0.516

Gnomad FIN exome

AF:

0.617

Gnomad NFE exome

AF:

0.615

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.621

AC:

904366

AN:

1456084

Hom.:

282782

Cov.:

AF XY:

0.617

AC XY:

447061

AN XY:

724204

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.588

Gnomad4 ASJ exome

AF:

0.575

Gnomad4 EAS exome

AF:

0.735

Gnomad4 SAS exome

AF:

0.512

Gnomad4 FIN exome

AF:

0.614

Gnomad4 NFE exome

AF:

0.624

Gnomad4 OTH exome

AF:

0.624

GnomAD4 genome

AF:

0.654

AC:

99470

AN:

152042

Hom.:

32878

Cov.:

AF XY:

0.651

AC XY:

48406

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.750

Gnomad4 AMR

AF:

0.612

Gnomad4 ASJ

AF:

0.589

Gnomad4 EAS

AF:

0.747

Gnomad4 SAS

AF:

0.515

Gnomad4 FIN

AF:

0.618

Gnomad4 NFE

AF:

0.619

Gnomad4 OTH

AF:

0.632

Alfa

AF:

0.610

Hom.:

12745

Bravo

AF:

0.659

Asia WGS

AF:

0.637

AC:

2214

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 25, 2014	- -

Cataract 11 multiple types

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Anterior segment dysgenesis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.96

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over