20-18012335-T-C

Variant names:

• chr20-18012335-T-C
• rs3748493

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.545 in 421,690 control chromosomes in the GnomAD database, including 64,256 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 0.57 (24801 hom., cov: 31)
  • Exomes 𝑓: 0.53 (39455 hom.)
• Consequence: PTMAP3 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 7 publications found

Genes affected

PTMAP3 (HGNC:9626): (prothymosin alpha pseudogene 3)

OVOL2 (HGNC:15804): (ovo like zinc finger 2) This gene encodes a member of the evolutionarily conserved ovo-like protein family. Mammalian members of this family contain a single zinc finger domain composed of a tetrad of C2H2 zinc fingers with variable N- and C-terminal extensions that contain intrinsically disordered domains. Members of this family are involved in epithelial development and differentiation. Knockout of this gene in mouse results in early embryonic lethality with phenotypes that include neurectoderm expansion, impaired vascularization, and heart anomalies. In humans, allelic variants of this gene have been associated with posterior polymorphous corneal dystrophy. [provided by RefSeq, Apr 2016]

OVOL2 Gene-Disease associations (from GenCC):

• posterior polymorphous corneal dystrophy 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital hereditary endothelial dystrophy type I

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• posterior polymorphous corneal dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000486776.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OVOL2	ENST00000486776.5	TSL:3	n.300-15583A>G		intron	N/A
	PTMAP3	ENST00000447474.1	TSL:6	n.*51T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.567 AC: 85956 AN: 151598 Hom.: 24761 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.533 AC: 143935 AN: 269972 Hom.: 39455 AF XY: 0.539 AC XY: 82285 AN XY: 152760

African (AFR) AF: 0.677 AC: 4618 AN: 6818

American (AMR) AF: 0.400 AC: 7723 AN: 19288

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 4391 AN: 7014

East Asian (EAS) AF: 0.467 AC: 4540 AN: 9730

South Asian (SAS) AF: 0.593 AC: 28640 AN: 48330

European-Finnish (FIN) AF: 0.551 AC: 11777 AN: 21374

Middle Eastern (MID) AF: 0.601 AC: 561 AN: 934

European-Non Finnish (NFE) AF: 0.521 AC: 74935 AN: 143896

Other (OTH) AF: 0.536 AC: 6750 AN: 12588

GnomAD4 genome AF: 0.567 AC: 86038 AN: 151718 Hom.: 24801 Cov.: 31 AF XY: 0.570 AC XY: 42294 AN XY: 74148

African (AFR) AF: 0.667 AC: 27516 AN: 41242

American (AMR) AF: 0.501 AC: 7650 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2198 AN: 3462

East Asian (EAS) AF: 0.467 AC: 2396 AN: 5128

South Asian (SAS) AF: 0.595 AC: 2863 AN: 4808

European-Finnish (FIN) AF: 0.553 AC: 5836 AN: 10552

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35634 AN: 67936

Other (OTH) AF: 0.569 AC: 1199 AN: 2108

Alfa AF: 0.539 Hom.: 47820

Bravo AF: 0.563

Asia WGS AF: 0.553 AC: 1925 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.10
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs3748493; hg19: chr20-17992979;