10-102238914-A-T

Position:

• chr10-102238914-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000370002.8(PITX3):​c.-13+2419T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,026 control chromosomes in the GnomAD database, including 33,417 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (33417 hom., cov: 31)
• Consequence: PITX3 ENST00000370002.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

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]

GBF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITX3	NM_005029.4	c.-13+2419T>A		intron_variant		ENST00000370002.8	NP_005020.1
GBF1	NM_001391923.1	c.-11+7998A>T		intron_variant			NP_001378852.1
GBF1	NM_001391924.1	c.-148-6730A>T		intron_variant			NP_001378853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITX3	ENST00000370002.8	c.-13+2419T>A		intron_variant		1	NM_005029.4	ENSP00000359019	P1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100111 AN: 151908 Hom.: 33362 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.630

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.659 AC: 100225 AN: 152026 Hom.: 33417 Cov.: 31 AF XY: 0.656 AC XY: 48728 AN XY: 74288

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.635

Alfa AF: 0.648 Hom.: 3979

Bravo AF: 0.664

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4919621; hg19: chr10-103998671;