14-71114061-G-A

Position:

• chr14-71114061-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014982.3(PCNX1):​c.*4126G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,830 control chromosomes in the GnomAD database, including 17,146 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (17145 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: PCNX1 NM_014982.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

Genes affected

PCNX1 (HGNC:19740): (pecanex 1) This gene encodes an evolutionarily conserved transmembrane protein similar to the pecanex protein in Drosophila. The fly protein is a component of the Notch signaling pathway, which functions in several developmental processes. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNX1	NM_014982.3	c.*4126G>A		3_prime_UTR_variant	36/36	ENST00000304743.7	NP_055797.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNX1	ENST00000304743.7	c.*4126G>A		3_prime_UTR_variant	36/36	1	NM_014982.3	ENSP00000304192.2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70058 AN: 151712 Hom.: 17133 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.462 AC: 70097 AN: 151828 Hom.: 17145 Cov.: 31 AF XY: 0.462 AC XY: 34258 AN XY: 74218

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.453

Alfa AF: 0.517 Hom.: 20234

Bravo AF: 0.436

Asia WGS AF: 0.451 AC: 1566 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs221924; hg19: chr14-71580778;