NM_015027.4:c.541G>T

Variant names:

• chr16-15006545-G-T
• NM_015027.4:c.541G>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015027.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXDC1	NM_015027.4	MANE Select	c.541G>T	p.Ala181Ser	missense	Exon 6 of 23	NP_055842.2	Q6P996-1
	PDXDC1	NM_001324019.2		c.538G>T	p.Ala180Ser	missense	Exon 6 of 23	NP_001310948.1
	PDXDC1	NM_001285447.1		c.496G>T	p.Ala166Ser	missense	Exon 6 of 23	NP_001272376.1	B4DHL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXDC1	ENST00000396410.9	TSL:1 MANE Select	c.541G>T	p.Ala181Ser	missense	Exon 6 of 23	ENSP00000379691.4	Q6P996-1
	PDXDC1	ENST00000569715.5	TSL:1	c.460G>T	p.Ala154Ser	missense	Exon 5 of 22	ENSP00000455070.1	Q6P996-5
	PDXDC1	ENST00000535621.6	TSL:1	c.541G>T	p.Ala181Ser	missense	Exon 6 of 17	ENSP00000437835.2	Q86XE2

Frequencies

GnomAD3 genomes Cov.: 47

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 47

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.21
Sift	Benign	0.37	T
Sift4G	Benign	0.099	T
Polyphen		0.86	P
Vest4		0.41
MutPred		0.75		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

Other links and lift over

hg19: chr16-15100402;