16-15004190-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015027.4(PDXDC1):c.246C>G(p.Ile82Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,452,812 control chromosomes in the GnomAD database, including 18,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (1917 hom., cov: 51)
  • Exomes 𝑓: 0.25 (16774 hom.)
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.86

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 (MetaRNN=0.0016328692).
• BP6: Variant 16-15004190-C-G is Benign according to our data. Variant chr16-15004190-C-G is described in ClinVar as [Benign]. Clinvar id is 768753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDXDC1	NM_015027.4	c.246C>G	p.Ile82Met	missense_variant	5/23	ENST00000396410.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDXDC1	ENST00000396410.9	c.246C>G	p.Ile82Met	missense_variant	5/23	1	NM_015027.4	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 36517 AN: 145896 Hom.: 1901 Cov.: 51

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.258

GnomAD3 exomes AF: 0.303 AC: 72679 AN: 239652 Hom.: 6576 AF XY: 0.298 AC XY: 38619 AN XY: 129484

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.464

Gnomad SAS exome AF: 0.341

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.246 AC: 322105 AN: 1306792 Hom.: 16774 Cov.: 35 AF XY: 0.250 AC XY: 163094 AN XY: 653256

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.511

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.250 AC: 36577 AN: 146020 Hom.: 1917 Cov.: 51 AF XY: 0.257 AC XY: 18342 AN XY: 71416

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.265

Alfa AF: 0.184 Hom.: 100

ExAC AF: 0.304 AC: 36885

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 07, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	14
Dann	Benign	0.81
DEOGEN2	Benign	0.0024	T;T;T;.;T;.;.;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.49	T;T;.;.;T;T;T;.;T
MetaRNN	Benign	0.0016	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	0.12	P;P;P;P;P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.22	N;N;N;N;N;N;.;.;N
Sift	Benign	0.18	T;T;T;T;T;T;.;.;T
Sift4G	Benign	0.49	T;T;T;T;T;T;T;T;T
Polyphen		0.0050, 0.048	.;.;B;B;B;.;.;.;.
Vest4		0.12
MPC		0.11
ClinPred		0.0013	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.037
gMVP		0.13

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: rs11549900; hg19: chr16-15098047; COSMIC: COSV57903506;