rs425565

Variant names:

• chr14-60137165-G-C
• rs425565
• NM_001330177.2:c.*2944G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330177.2(PCNX4):​c.*2944G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,096 control chromosomes in the GnomAD database, including 6,897 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 0.25 (6897 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCNX4 NM_001330177.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 3 publications found

Genes affected

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX4	NM_001330177.2	c.*2944G>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000406854.6	NP_001317106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX4	ENST00000406854.6	c.*2944G>C		3_prime_UTR_variant	Exon 11 of 11	5	NM_001330177.2	ENSP00000384801.1
PCNX4	ENST00000317623.8	c.*2944G>C		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000317396.4
PCNX4	ENST00000406949.5	c.2565+11342G>C		intron_variant	Intron 9 of 9	2		ENSP00000385201.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38121 AN: 151976 Hom.: 6865 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.0925

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.243

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 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: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.251 AC: 38205 AN: 152096 Hom.: 6897 Cov.: 32 AF XY: 0.252 AC XY: 18723 AN XY: 74366

African (AFR) AF: 0.504 AC: 20913 AN: 41462

American (AMR) AF: 0.172 AC: 2637 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1671 AN: 5166

South Asian (SAS) AF: 0.348 AC: 1677 AN: 4816

European-Finnish (FIN) AF: 0.100 AC: 1060 AN: 10594

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8935 AN: 67986

Other (OTH) AF: 0.242 AC: 511 AN: 2110

Alfa AF: 0.194 Hom.: 544

Bravo AF: 0.262

Asia WGS AF: 0.353 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.3
DANN	Benign	0.86
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs425565; hg19: chr14-60603883;