rs1409538615

Variant names:

• chr16-15026668-T-C
• rs1409538615
• NM_015027.4:c.1166T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015027.4(PDXDC1):​c.1166T>C​(p.Val389Ala) variant causes a missense change. 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: 51)
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.16
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.866

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.1166T>C	p.Val389Ala	missense	Exon 14 of 23	NP_055842.2	Q6P996-1
	PDXDC1	NM_001324019.2		c.1163T>C	p.Val388Ala	missense	Exon 14 of 23	NP_001310948.1
	PDXDC1	NM_001285447.1		c.1121T>C	p.Val374Ala	missense	Exon 14 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.1166T>C	p.Val389Ala	missense	Exon 14 of 23	ENSP00000379691.4	Q6P996-1
	PDXDC1	ENST00000569715.5	TSL:1	c.1085T>C	p.Val362Ala	missense	Exon 13 of 22	ENSP00000455070.1	Q6P996-5
	PDXDC1	ENST00000535621.6	TSL:1	c.1166T>C	p.Val389Ala	missense	Exon 14 of 17	ENSP00000437835.2	Q86XE2

Frequencies

GnomAD3 genomes Cov.: 51

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 51

Alfa AF: 0.00 Hom.: 0

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	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.9	L
PhyloP100		7.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.30
Sift	Benign	0.044	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.74		Gain of sheet (P = 0.1208)
MVP		0.68
MPC		0.73
ClinPred		0.91	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

dbSNP: rs1409538615; hg19: chr16-15120525;