16-15016220-C-T

Position:

• chr16-15016220-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The ENST00000396410.9(PDXDC1):​c.812+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (365 hom., cov: 53)
  • Exomes 𝑓: 0.46 (3147 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDXDC1 ENST00000396410.9 splice_region, intron
• Scores: Splicing: ADA: 0.0002343
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.972

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-15016220-C-T is Benign according to our data. Variant chr16-15016220-C-T is described in ClinVar as [Benign]. Clinvar id is 768754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDXDC1	NM_015027.4	c.812+7C>T		splice_region_variant, intron_variant		ENST00000396410.9	NP_055842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDXDC1	ENST00000396410.9	c.812+7C>T		splice_region_variant, intron_variant		1	NM_015027.4	ENSP00000379691	P1
	ENST00000617759.1	n.171G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 61143 AN: 146420 Hom.: 366 Cov.: 53 FAILED QC

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.443

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.457 AC: 638762 AN: 1396430 Hom.: 3147 Cov.: 110 AF XY: 0.457 AC XY: 318010 AN XY: 695268

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.452

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.452

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.417 AC: 61167 AN: 146538 Hom.: 365 Cov.: 53 AF XY: 0.416 AC XY: 29784 AN XY: 71614

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.439

Alfa AF: 0.444 Hom.: 53

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 07, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4262938; hg19: chr16-15110077; COSMIC: COSV57904937;