rs3748493

Positions:

• chr20-18012335-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTMAP3		n.18012335T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OVOL2	ENST00000486776.5	n.300-15583A>G		intron_variant		3

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

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.536

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

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.553

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.569

Alfa AF: 0.531 Hom.: 25933

Bravo AF: 0.563

Asia WGS AF: 0.553 AC: 1925 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3748493; hg19: chr20-17992979;