rs2281983

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005029.4(PITX3):c.285C>T(p.Ile95Ile) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. I95I) has been classified as Likely 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

Publications

42 publications found

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:4181): (golgi brefeldin A resistant guanine nucleotide exchange factor 1) This gene encodes a member of the Sec7 domain family. The encoded protein is a guanine nucleotide exchange factor that regulates the recruitment of proteins to membranes by mediating GDP to GTP exchange. The encoded protein is localized to the Golgi apparatus and plays a role in vesicular trafficking by activating ADP ribosylation factor 1. The encoded protein has also been identified as an important host factor for viral replication. Multiple transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

GBF1 Gene-Disease associations (from GenCC):

axonal neuropathy
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox

GBF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 196404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein
PITX3	NM_005029.4 link	c.285C>T	p.Ile95Ile	synonymous_variant	Exon 3 of 4	ENST00000370002.8	NP_005020.1
PITX3	XM_047425352.1 link	c.285C>T	p.Ile95Ile	synonymous_variant	Exon 2 of 3		XP_047281308.1
GBF1	NM_001391923.1 link	c.-11+708G>A		intron_variant	Intron 1 of 39		NP_001378852.1
GBF1	NM_001391924.1 link	c.-149+708G>A		intron_variant	Intron 1 of 40		NP_001378853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITX3	ENST00000370002.8 link	c.285C>T	p.Ile95Ile	synonymous_variant	Exon 3 of 4	1	NM_005029.4	ENSP00000359019.3		O75364

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

GnomAD2 exomes

AF:

0.617

AC:

148912

AN:

241510

AF XY:

0.609

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 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

African (AFR)

AF:

0.753

AC:

25147

AN:

33406

American (AMR)

AF:

0.588

AC:

25909

AN:

44066

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

14953

AN:

26012

East Asian (EAS)

AF:

0.735

AC:

29080

AN:

39548

South Asian (SAS)

AF:

0.512

AC:

43829

AN:

85600

European-Finnish (FIN)

AF:

0.614

AC:

32501

AN:

52914

Middle Eastern (MID)

AF:

0.551

AC:

3114

AN:

5648

European-Non Finnish (NFE)

AF:

0.624

AC:

692303

AN:

1108746

Other (OTH)

AF:

0.624

AC:

37530

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16561

33122

49684

66245

82806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18594

37188

55782

74376

92970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.654

AC:

99470

AN:

152042

Hom.:

32878

Cov.:

AF XY:

0.651

AC XY:

48406

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.750

AC:

31135

AN:

41510

American (AMR)

AF:

0.612

AC:

9357

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.589

AC:

2044

AN:

3470

East Asian (EAS)

AF:

0.747

AC:

3839

AN:

5138

South Asian (SAS)

AF:

0.515

AC:

2487

AN:

4828

European-Finnish (FIN)

AF:

0.618

AC:

6533

AN:

10576

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42034

AN:

67910

Other (OTH)

AF:

0.632

AC:

1335

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1760

3520

5280

7040

8800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.612

Hom.:

12964

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Aug 25, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cataract 11 multiple types

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Anterior segment dysgenesis 1

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

-0.21

PromoterAI

-0.054

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over