rs221924

Variant names:

• chr14-71114061-G-A
• rs221924
• NM_014982.3:c.*4126G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ENSG00000286423 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014982.3. 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
	PCNX1	NM_014982.3	MANE Select	c.*4126G>A		3_prime_UTR	Exon 36 of 36	NP_055797.2
	PCNX1	NM_001308160.2		c.*4126G>A		3_prime_UTR	Exon 34 of 34	NP_001295089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX1	ENST00000304743.7	TSL:1 MANE Select	c.*4126G>A		3_prime_UTR	Exon 36 of 36	ENSP00000304192.2
	ENSG00000286423	ENST00000840006.1		n.987-19301C>T		intron	N/A
	ENSG00000286423	ENST00000840007.1		n.955-19301C>T		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.340 AC: 14076 AN: 41378

American (AMR) AF: 0.362 AC: 5521 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1621 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1312 AN: 5164

South Asian (SAS) AF: 0.536 AC: 2575 AN: 4808

European-Finnish (FIN) AF: 0.566 AC: 5964 AN: 10540

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.551 AC: 37442 AN: 67920

Other (OTH) AF: 0.453 AC: 954 AN: 2108

Alfa AF: 0.502 Hom.: 28580

Bravo AF: 0.436

Asia WGS AF: 0.451 AC: 1566 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.77
PhyloP100		-0.24
Mutation Taster		=100/0	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: rs221924; hg19: chr14-71580778;