rs7200543

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 65 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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXDC1	NM_015027.4	MANE Select	c.2205A>G	p.Leu735Leu	synonymous	Exon 23 of 23	NP_055842.2	Q6P996-1
	PDXDC1	NM_001324019.2		c.2202A>G	p.Leu734Leu	synonymous	Exon 23 of 23	NP_001310948.1
	PDXDC1	NM_001285447.1		c.2160A>G	p.Leu720Leu	synonymous	Exon 23 of 23	NP_001272376.1	B4DHL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXDC1	ENST00000396410.9	TSL:1 MANE Select	c.2205A>G	p.Leu735Leu	synonymous	Exon 23 of 23	ENSP00000379691.4	Q6P996-1
	PDXDC1	ENST00000569715.5	TSL:1	c.2124A>G	p.Leu708Leu	synonymous	Exon 22 of 22	ENSP00000455070.1	Q6P996-5
	PDXDC1	ENST00000535621.6	TSL:1	c.1399+6057A>G		intron	N/A	ENSP00000437835.2	Q86XE2

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

GnomAD2 exomes AF: 0.351 AC: 88253 AN: 251272 AF XY: 0.346

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 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

African (AFR) AF: 0.224 AC: 7507 AN: 33480

American (AMR) AF: 0.534 AC: 23881 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 8353 AN: 26132

East Asian (EAS) AF: 0.422 AC: 16758 AN: 39700

South Asian (SAS) AF: 0.381 AC: 32875 AN: 86254

European-Finnish (FIN) AF: 0.325 AC: 17318 AN: 53362

Middle Eastern (MID) AF: 0.277 AC: 1595 AN: 5768

European-Non Finnish (NFE) AF: 0.299 AC: 332217 AN: 1111854

Other (OTH) AF: 0.320 AC: 19342 AN: 60382

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

African (AFR) AF: 0.223 AC: 9258 AN: 41492

American (AMR) AF: 0.442 AC: 6748 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1997 AN: 5172

South Asian (SAS) AF: 0.404 AC: 1952 AN: 4826

European-Finnish (FIN) AF: 0.339 AC: 3587 AN: 10576

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20681 AN: 67960

Other (OTH) AF: 0.324 AC: 683 AN: 2110

Alfa AF: 0.308 Hom.: 32849

Bravo AF: 0.311

Asia WGS AF: 0.432 AC: 1502 AN: 3478

EpiCase AF: 0.294

EpiControl AF: 0.295

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	PDXDC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		0.52
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: rs7200543; hg19: chr16-15129970; COSMIC: COSV55074325; COSMIC: COSV55074325;