16-14998392-C-A

Variant names:

• chr16-14998392-C-A
• NM_015027.4:c.148C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015027.4(PDXDC1):​c.148C>A​(p.Pro50Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 49)
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35950878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDXDC1	NM_015027.4	c.148C>A	p.Pro50Thr	missense_variant	Exon 3 of 23	ENST00000396410.9	NP_055842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDXDC1	ENST00000396410.9	c.148C>A	p.Pro50Thr	missense_variant	Exon 3 of 23	1	NM_015027.4	ENSP00000379691.4

Frequencies

GnomAD3 genomes Cov.: 49

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 49

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.148C>A (p.P50T) alteration is located in exon 3 (coding exon 3) of the PDXDC1 gene. This alteration results from a C to A substitution at nucleotide position 148, causing the proline (P) at amino acid position 50 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;T;.;T;.;.;T;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;.;.;D;D;D;.;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.36	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.6	.;.;.;L;L;L;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D;D;.;.;D;.
REVEL	Benign	0.17
Sift	Benign	0.078	T;D;T;T;T;D;.;.;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D
Polyphen		1.0, 0.59	.;.;D;P;D;.;.;.;.;.
Vest4		0.56
MutPred		0.085		.;.;Gain of phosphorylation at P50 (P = 0.0833);Gain of phosphorylation at P50 (P = 0.0833);Gain of phosphorylation at P50 (P = 0.0833);Gain of phosphorylation at P50 (P = 0.0833);.;Gain of phosphorylation at P50 (P = 0.0833);.;.;
MVP		0.76
MPC		0.55
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.39
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-15092249;