16-15017324-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015027.4(PDXDC1):c.865G>A(p.Ala289Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 47)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDXDC1	NM_015027.4	c.865G>A	p.Ala289Thr	missense_variant	11/23	ENST00000396410.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDXDC1	ENST00000396410.9	c.865G>A	p.Ala289Thr	missense_variant	11/23	1	NM_015027.4	P1

Frequencies

GnomAD3 genomes Cov.: 47

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1 AN: 1457350 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725292

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 47

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

Oct 06, 2021

The c.865G>A (p.A289T) alteration is located in exon 11 (coding exon 11) of the PDXDC1 gene. This alteration results from a G to A substitution at nucleotide position 865, causing the alanine (A) at amino acid position 289 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	Benign	0.22
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Benign	-0.11
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.038	T;T;.;T;.;.;T;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D;.;.;D;D;D;.;D;D
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.62	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N;N;N;N;N;.;.;N;.
Sift	Benign	0.046	D;D;D;D;D;.;.;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D;D;D
Polyphen		1.0, 0.54	.;D;P;D;.;.;.;.;.
Vest4		0.48
MutPred		0.38		.;Gain of glycosylation at A289 (P = 0.0435);.;Gain of glycosylation at A289 (P = 0.0435);.;.;Gain of glycosylation at A289 (P = 0.0435);.;.;
MVP		0.66
MPC		0.51
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.22
gMVP		0.46

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: chr16-15111181;