NM_015027.4:c.131C>G

Variant names:

• chr16-14998375-C-G
• rs369615560
• NM_015027.4:c.131C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015027.4(PDXDC1):​c.131C>G​(p.Ser44Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S44Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 49)
  • Exomes 𝑓: 0.000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1981188).

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.131C>G	p.Ser44Cys	missense	Exon 3 of 23	NP_055842.2	Q6P996-1
	PDXDC1	NM_001324019.2		c.128C>G	p.Ser43Cys	missense	Exon 3 of 23	NP_001310948.1
	PDXDC1	NM_001285447.1		c.86C>G	p.Ser29Cys	missense	Exon 3 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.131C>G	p.Ser44Cys	missense	Exon 3 of 23	ENSP00000379691.4	Q6P996-1
	PDXDC1	ENST00000569715.5	TSL:1	c.131C>G	p.Ser44Cys	missense	Exon 3 of 22	ENSP00000455070.1	Q6P996-5
	PDXDC1	ENST00000535621.6	TSL:1	c.131C>G	p.Ser44Cys	missense	Exon 3 of 17	ENSP00000437835.2	Q86XE2

Frequencies

GnomAD3 genomes Cov.: 49

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250464 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000157 AC: 23 AN: 1460970 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726824

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

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111748

Other (OTH) AF: 0.0000497 AC: 3 AN: 60354

⚠️ 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 Cov.: 49

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.9
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.062
Sift	Benign	0.035	D
Sift4G	Uncertain	0.052	T
Polyphen		0.81	P
Vest4		0.29
MVP		0.53
MPC		0.26
ClinPred		0.34	T
GERP RS		4.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.12
gMVP		0.28
Mutation Taster		=80/20	polymorphism

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

dbSNP: rs369615560; hg19: chr16-15092232;