10-102232842-C-T

Position:

• chr10-102232842-C-T

Variant summary

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

The NM_005029.4(PITX3):​c.-12-750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,094 control chromosomes in the GnomAD database, including 32,997 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 (32997 hom., cov: 33)
• Consequence: PITX3 NM_005029.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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: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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITX3	NM_005029.4	c.-12-750G>A		intron_variant		ENST00000370002.8	NP_005020.1
GBF1	NM_001391923.1	c.-11+1926C>T		intron_variant			NP_001378852.1
GBF1	NM_001391924.1	c.-149+1926C>T		intron_variant			NP_001378853.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITX3	ENST00000370002.8	c.-12-750G>A		intron_variant		1	NM_005029.4	ENSP00000359019.3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99587 AN: 151974 Hom.: 32952 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.655 AC: 99689 AN: 152094 Hom.: 32997 Cov.: 33 AF XY: 0.652 AC XY: 48485 AN XY: 74324

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.632

Alfa AF: 0.637 Hom.: 6840

Bravo AF: 0.660

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.046
DANN	Benign	0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3758553; hg19: chr10-103992599;