chr10-102232842-C-T

Variant names:

• chr10-102232842-C-T
• rs3758553
• NM_005029.4:c.-12-750G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

GBF1 Gene-Disease associations (from GenCC):

• axonal neuropathy

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005029.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITX3	NM_005029.4	MANE Select	c.-12-750G>A		intron	N/A	NP_005020.1	O75364
	GBF1	NM_001391923.1		c.-11+1926C>T		intron	N/A	NP_001378852.1	Q92538-2
	GBF1	NM_001391924.1		c.-149+1926C>T		intron	N/A	NP_001378853.1	Q92538-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITX3	ENST00000370002.8	TSL:1 MANE Select	c.-12-750G>A		intron	N/A	ENSP00000359019.3	O75364

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

African (AFR) AF: 0.752 AC: 31227 AN: 41500

American (AMR) AF: 0.613 AC: 9354 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 2041 AN: 3464

East Asian (EAS) AF: 0.748 AC: 3870 AN: 5176

South Asian (SAS) AF: 0.518 AC: 2499 AN: 4828

European-Finnish (FIN) AF: 0.619 AC: 6552 AN: 10578

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42108 AN: 67976

Other (OTH) AF: 0.632 AC: 1331 AN: 2106

Alfa AF: 0.640 Hom.: 7061

Bravo AF: 0.660

Asia WGS AF: 0.638 AC: 2220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.046
DANN	Benign	0.16
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3758553; hg19: chr10-103992599;