chr16-15008813-C-A

Variant names:

• chr16-15008813-C-A
• rs150502355
• NM_015027.4:c.614C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_015027.4(PDXDC1):​c.614C>A​(p.Pro205His) variant causes a missense change. The variant allele was found at a frequency of 0.000511 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., cov: 41)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 7.18
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018517315).
• BP6: Variant 16-15008813-C-A is Benign according to our data. Variant chr16-15008813-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 790700.

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.614C>A	p.Pro205His	missense	Exon 7 of 23	NP_055842.2	Q6P996-1
	PDXDC1	NM_001324019.2		c.611C>A	p.Pro204His	missense	Exon 7 of 23	NP_001310948.1
	PDXDC1	NM_001285447.1		c.569C>A	p.Pro190His	missense	Exon 7 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.614C>A	p.Pro205His	missense	Exon 7 of 23	ENSP00000379691.4	Q6P996-1
	PDXDC1	ENST00000569715.5	TSL:1	c.533C>A	p.Pro178His	missense	Exon 6 of 22	ENSP00000455070.1	Q6P996-5
	PDXDC1	ENST00000535621.6	TSL:1	c.614C>A	p.Pro205His	missense	Exon 7 of 17	ENSP00000437835.2	Q86XE2

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 465 AN: 152074 Hom.: 0 Cov.: 41

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000638 AC: 160 AN: 250904 AF XY: 0.000413

Gnomad AFR exome AF: 0.00913

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000238 AC: 348 AN: 1461240 Hom.: 0 Cov.: 31 AF XY: 0.000197 AC XY: 143 AN XY: 726974

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00870 AC: 289 AN: 33214

American (AMR) AF: 0.000381 AC: 17 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111806

Other (OTH) AF: 0.000630 AC: 38 AN: 60348

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00313 AC: 476 AN: 152190 Hom.: 0 Cov.: 41 AF XY: 0.00305 AC XY: 227 AN XY: 74418

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0112 AC: 465 AN: 41434

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68048

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00173 Hom.: 0

ESP6500AA AF: 0.0121 AC: 53

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00126 AC: 153

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-7.4	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.92
MVP		0.86
MPC		0.56
ClinPred		0.11	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.69
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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

dbSNP: rs150502355; hg19: chr16-15102670;