rs7200543

Variant names:

• chr16-15036113-A-G
• rs7200543
• NM_015027.4:c.2205A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_015027.4(PDXDC1):​c.2205A>G​(p.Leu735Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,730 control chromosomes in the GnomAD database, including 82,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.30 (7527 hom., cov: 32)
  • Exomes 𝑓: 0.31 (75023 hom.)
• Consequence: PDXDC1 NM_015027.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.524

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-15036113-A-G is Benign according to our data. Variant chr16-15036113-A-G is described in ClinVar as [Benign]. Clinvar id is 3059969.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.524 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXDC1	NM_015027.4	c.2205A>G	p.Leu735Leu	synonymous_variant	Exon 23 of 23	ENST00000396410.9	NP_055842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDXDC1	ENST00000396410.9	c.2205A>G	p.Leu735Leu	synonymous_variant	Exon 23 of 23	1	NM_015027.4	ENSP00000379691.4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46238 AN: 151960 Hom.: 7505 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.318

GnomAD3 exomes AF: 0.351 AC: 88253 AN: 251272 Hom.: 16788 AF XY: 0.346 AC XY: 46983 AN XY: 135804

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.544

Gnomad ASJ exome AF: 0.323

Gnomad EAS exome AF: 0.403

Gnomad SAS exome AF: 0.385

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.335

GnomAD4 exome AF: 0.315 AC: 459846 AN: 1461652 Hom.: 75023 Cov.: 39 AF XY: 0.316 AC XY: 229825 AN XY: 727150

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.305 AC: 46308 AN: 152078 Hom.: 7527 Cov.: 32 AF XY: 0.310 AC XY: 23073 AN XY: 74334

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.324

Alfa AF: 0.309 Hom.: 16440

Bravo AF: 0.311

Asia WGS AF: 0.432 AC: 1502 AN: 3478

EpiCase AF: 0.294

EpiControl AF: 0.295

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

PDXDC1-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.69

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: rs7200543; hg19: chr16-15129970; COSMIC: COSV55074325; COSMIC: COSV55074325;