16-15006545-G-T

Variant summary

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

The NM_015027.4(PDXDC1):c.541G>T(p.Ala181Ser) 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)
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

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.541G>T	p.Ala181Ser	missense_variant	6/23	ENST00000396410.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDXDC1	ENST00000396410.9	c.541G>T	p.Ala181Ser	missense_variant	6/23	1	NM_015027.4	P1

Frequencies

GnomAD3 genomes Cov.: 47

GnomAD4 exome Cov.: 32

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

Dec 20, 2023

The c.541G>T (p.A181S) alteration is located in exon 6 (coding exon 6) of the PDXDC1 gene. This alteration results from a G to T substitution at nucleotide position 541, causing the alanine (A) at amino acid position 181 to be replaced by a serine (S). 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	0.14
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T;.;T;.;.;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D;.;.;D;D;D;.;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.51	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N;N;N;N;N;.;.;N;.
Sift	Benign	0.37	T;T;T;T;T;.;.;T;.
Sift4G	Benign	0.099	T;T;T;T;T;T;T;T;T
Polyphen		0.86, 0.57, 0.97	.;P;P;D;.;.;.;.;.
Vest4		0.41
MutPred		0.75		.;Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;.;Loss of helix (P = 0.1299);.;.;
MVP		0.54
MPC		0.18
ClinPred		0.80	D
GERP RS		5.7
Varity_R		0.14
gMVP		0.44

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: chr16-15100402;