chr16-14989008-C-T

Variant names:

• chr16-14989008-C-T
• rs4985167
• NM_015027.4:c.22-8745C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BS2: High Homozygotes in GnomAd4 at 2156 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015027.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXDC1	NM_015027.4	MANE Select	c.22-8745C>T		intron	N/A	NP_055842.2
	PDXDC1	NM_001324019.2		c.22-8745C>T		intron	N/A	NP_001310948.1
	PDXDC1	NM_001285447.1		c.-24-8745C>T		intron	N/A	NP_001272376.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXDC1	ENST00000396410.9	TSL:1 MANE Select	c.22-8745C>T		intron	N/A	ENSP00000379691.4
	PDXDC1	ENST00000569715.5	TSL:1	c.22-8745C>T		intron	N/A	ENSP00000455070.1
	PDXDC1	ENST00000535621.6	TSL:1	c.22-8745C>T		intron	N/A	ENSP00000437835.2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.180 AC: 5921 AN: 32816

American (AMR) AF: 0.464 AC: 20364 AN: 43914

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 7396 AN: 25506

East Asian (EAS) AF: 0.510 AC: 20137 AN: 39520

South Asian (SAS) AF: 0.338 AC: 28677 AN: 84760

European-Finnish (FIN) AF: 0.279 AC: 14530 AN: 52024

Middle Eastern (MID) AF: 0.225 AC: 1266 AN: 5618

European-Non Finnish (NFE) AF: 0.242 AC: 256721 AN: 1059396

Other (OTH) AF: 0.273 AC: 15947 AN: 58410

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.179 AC: 7241 AN: 40530

American (AMR) AF: 0.369 AC: 5432 AN: 14720

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 968 AN: 3398

East Asian (EAS) AF: 0.451 AC: 2302 AN: 5100

South Asian (SAS) AF: 0.357 AC: 1672 AN: 4684

European-Finnish (FIN) AF: 0.291 AC: 2981 AN: 10240

Middle Eastern (MID) AF: 0.180 AC: 51 AN: 284

European-Non Finnish (NFE) AF: 0.249 AC: 16257 AN: 65260

Other (OTH) AF: 0.271 AC: 545 AN: 2014

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.259 Hom.: 168

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.93
PhyloP100		5.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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