16-14989008-C-T

Position:

• chr16-14989008-C-T

Variant summary

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

The NM_015027.4(PDXDC1):​c.22-8745C>T variant causes a intron change. The variant allele was found at a frequency of 0.264 in 1,549,084 control chromosomes in the GnomAD database, including 21,341 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 0.26 (2156 hom., cov: 52)
  • Exomes 𝑓: 0.26 (19185 hom.)
• Consequence: PDXDC1 NM_015027.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.10

Genes affected

PDXDC1 (HGNC:28995): (pyridoxal dependent decarboxylase domain containing 1) Enables cadherin binding activity. Predicted to be involved in carboxylic acid metabolic process. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261819 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXDC1	NM_015027.4	c.22-8745C>T		intron_variant		ENST00000396410.9	NP_055842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXDC1	ENST00000396410.9	c.22-8745C>T		intron_variant		1	NM_015027.4	ENSP00000379691.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 37583 AN: 147006 Hom.: 2141 Cov.: 52

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.265 AC: 370959 AN: 1401964 Hom.: 19185 Cov.: 85 AF XY: 0.267 AC XY: 186248 AN XY: 698510

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.256 AC: 37639 AN: 147120 Hom.: 2156 Cov.: 52 AF XY: 0.262 AC XY: 18851 AN XY: 71884

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.271

Alfa AF: 0.259 Hom.: 168

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4985167; hg19: chr16-15082865; COSMIC: COSV57904612;