Variant 10-102230772-GC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_005029.4(PITX3):c.650del(p.Gly217AlafsTer92) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

PITX3
NM_005029.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 1.25

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.285 CDS is truncated, and there are 1 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 10-102230772-GC-G is Pathogenic according to our data. Variant chr10-102230772-GC-G is described in ClinVar as [Pathogenic]. Clinvar id is 6939.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-102230772-GC-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PITX3	NM_005029.4 linkuse as main transcript	c.650del	p.Gly217AlafsTer92	frameshift_variant	4/4	ENST00000370002.8	NP_005020.1
PITX3	XM_047425352.1 linkuse as main transcript	c.650del	p.Gly217AlafsTer92	frameshift_variant	3/3		XP_047281308.1
GBF1	NM_001391923.1 linkuse as main transcript	c.-152del		5_prime_UTR_variant	1/40		NP_001378852.1
GBF1	NM_001391924.1 linkuse as main transcript	c.-290del		5_prime_UTR_variant	1/41		NP_001378853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITX3	ENST00000370002.8 linkuse as main transcript	c.650del	p.Gly217AlafsTer92	frameshift_variant	4/4	1	NM_005029.4	ENSP00000359019	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cataract 11, posterior polar

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2006

- -

Cataract 11, posterior polar, with microphthalmia and neurodevelopmental abnormalities

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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