16-15004190-C-G

Variant names:

• chr16-15004190-C-G
• rs11549900
• NM_015027.4:c.246C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015027.4(PDXDC1):​c.246C>G​(p.Ile82Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,452,812 control chromosomes in the GnomAD database, including 18,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (1917 hom., cov: 51)
  • Exomes 𝑓: 0.25 (16774 hom.)
• Consequence: PDXDC1 NM_015027.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.86
• Publications: 30 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016328692).
• BP6: Variant 16-15004190-C-G is Benign according to our data. Variant chr16-15004190-C-G is described in ClinVar as Benign. ClinVar VariationId is 768753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 1917 AR gene

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.246C>G	p.Ile82Met	missense	Exon 5 of 23	NP_055842.2	Q6P996-1
	PDXDC1	NM_001324019.2		c.243C>G	p.Ile81Met	missense	Exon 5 of 23	NP_001310948.1
	PDXDC1	NM_001285447.1		c.201C>G	p.Ile67Met	missense	Exon 5 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.246C>G	p.Ile82Met	missense	Exon 5 of 23	ENSP00000379691.4	Q6P996-1
	PDXDC1	ENST00000569715.5	TSL:1	c.165C>G	p.Ile55Met	missense	Exon 4 of 22	ENSP00000455070.1	Q6P996-5
	PDXDC1	ENST00000535621.6	TSL:1	c.246C>G	p.Ile82Met	missense	Exon 5 of 17	ENSP00000437835.2	Q86XE2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 36517 AN: 145896 Hom.: 1901 Cov.: 51

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.258

GnomAD2 exomes AF: 0.303 AC: 72679 AN: 239652 AF XY: 0.298

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.275

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.246 AC: 322105 AN: 1306792 Hom.: 16774 Cov.: 35 AF XY: 0.250 AC XY: 163094 AN XY: 653256

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

African (AFR) AF: 0.156 AC: 4979 AN: 31902

American (AMR) AF: 0.460 AC: 19831 AN: 43134

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 6600 AN: 24588

East Asian (EAS) AF: 0.511 AC: 19897 AN: 38962

South Asian (SAS) AF: 0.334 AC: 27421 AN: 82124

European-Finnish (FIN) AF: 0.279 AC: 14364 AN: 51526

Middle Eastern (MID) AF: 0.213 AC: 1141 AN: 5358

European-Non Finnish (NFE) AF: 0.219 AC: 213753 AN: 974260

Other (OTH) AF: 0.257 AC: 14119 AN: 54938

⚠️ 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: 0.250 AC: 36577 AN: 146020 Hom.: 1917 Cov.: 51 AF XY: 0.257 AC XY: 18342 AN XY: 71416

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

African (AFR) AF: 0.166 AC: 6733 AN: 40570

American (AMR) AF: 0.364 AC: 5322 AN: 14610

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 908 AN: 3360

East Asian (EAS) AF: 0.449 AC: 2282 AN: 5082

South Asian (SAS) AF: 0.357 AC: 1653 AN: 4632

European-Finnish (FIN) AF: 0.290 AC: 2935 AN: 10134

Middle Eastern (MID) AF: 0.200 AC: 58 AN: 290

European-Non Finnish (NFE) AF: 0.248 AC: 15984 AN: 64482

Other (OTH) AF: 0.265 AC: 532 AN: 2008

⚠️ 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: 0.184 Hom.: 100

ExAC AF: 0.304 AC: 36885

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.23	N
PhyloP100		1.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.10
Sift	Benign	0.18	T
Sift4G	Benign	0.49	T
Polyphen		0.0050	B
Vest4		0.12
MPC		0.11
ClinPred		0.0013	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.037
gMVP		0.13
Mutation Taster		=92/8	polymorphism (auto)

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: rs11549900; hg19: chr16-15098047; COSMIC: COSV57903506;