14-60115248-A-G

Variant names:

• chr14-60115248-A-G
• rs768159735
• NM_001330177.2:c.1144A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001330177.2(PCNX4):​c.1144A>G​(p.Ile382Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PCNX4 NM_001330177.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0213207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX4	NM_001330177.2	c.1144A>G	p.Ile382Val	missense_variant	Exon 4 of 11	ENST00000406854.6	NP_001317106.1
PCNX4	NM_022495.5	c.442A>G	p.Ile148Val	missense_variant	Exon 3 of 10		NP_071940.4
PCNX4	XM_047431699.1	c.1144A>G	p.Ile382Val	missense_variant	Exon 4 of 11		XP_047287655.1
PCNX4	XM_047431700.1	c.1144A>G	p.Ile382Val	missense_variant	Exon 4 of 10		XP_047287656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX4	ENST00000406854.6	c.1144A>G	p.Ile382Val	missense_variant	Exon 4 of 11	5	NM_001330177.2	ENSP00000384801.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000322 AC: 8 AN: 248824 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460578 Hom.: 0 Cov.: 49 AF XY: 0.00000688 AC XY: 5 AN XY: 726660

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.000246 AC: 11 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111106

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000497 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.8
DANN	Benign	0.24
DEOGEN2	Benign	0.0026	.;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.021	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;L;.
PhyloP100		1.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.040	N;N;N
REVEL	Benign	0.026
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0, 0.0010	.;B;B
Vest4		0.029
MutPred		0.17		.;Gain of sheet (P = 0.0344);.;
MVP		0.055
MPC		0.012
ClinPred		0.047	T
GERP RS		2.8
Varity_R		0.023
gMVP		0.17
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs768159735; hg19: chr14-60581966;