chr16-15028951-C-G

Position:

• chr16-15028951-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000396410.9(PDXDC1):​c.1278C>G​(p.Asp426Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 59)
• Consequence: PDXDC1 ENST00000396410.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.725

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXDC1	NM_015027.4	c.1278C>G	p.Asp426Glu	missense_variant	15/23	ENST00000396410.9	NP_055842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXDC1	ENST00000396410.9	c.1278C>G	p.Asp426Glu	missense_variant	15/23	1	NM_015027.4	ENSP00000379691	P1

Frequencies

GnomAD3 genomes Cov.: 59

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 59

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.1278C>G (p.D426E) alteration is located in exon 15 (coding exon 15) of the PDXDC1 gene. This alteration results from a C to G substitution at nucleotide position 1278, causing the aspartic acid (D) at amino acid position 426 to be replaced by a glutamic acid (E). 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	Uncertain	0.55
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	6.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;T;.;T;.;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.92	D;.;.;D;D;D;D
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.86	D;D;D;D;D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.4	.;.;.;M;.;.;.
MutationTaster	Benign	0.77	D;D;D;D;D;D;D;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D;N;N;D;D;.;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D;D;D;D;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0, 1.0	.;D;D;D;.;.;.
Vest4		0.77
MutPred		0.75		.;Loss of helix (P = 0.028);.;Loss of helix (P = 0.028);.;.;.;
MVP		0.41
MPC		0.58
ClinPred		0.98	D
GERP RS		-7.1
Varity_R		0.47
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr16-15122808;