rs150511705

Variant names:

• chr14-60121235-A-C
• NM_001330177.2:c.1982A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-60121235-A-C
• chr14-60121235-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001330177.2(PCNX4):​c.1982A>C​(p.Gln661Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q661R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PCNX4 NM_001330177.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.71

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX4	NM_001330177.2	c.1982A>C	p.Gln661Pro	missense_variant	Exon 8 of 11	ENST00000406854.6	NP_001317106.1
PCNX4	NM_022495.5	c.1280A>C	p.Gln427Pro	missense_variant	Exon 7 of 10		NP_071940.4
PCNX4	XM_047431699.1	c.1982A>C	p.Gln661Pro	missense_variant	Exon 8 of 11		XP_047287655.1
PCNX4	XM_047431700.1	c.1982A>C	p.Gln661Pro	missense_variant	Exon 8 of 10		XP_047287656.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX4	ENST00000406854.6	c.1982A>C	p.Gln661Pro	missense_variant	Exon 8 of 11	5	NM_001330177.2	ENSP00000384801.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455744 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 724250

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	2.9	.;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.039	D;D;T
Polyphen		0.95, 0.48	.;P;P
Vest4		0.77
MutPred		0.56		.;Loss of helix (P = 0.0237);.;
MVP		0.26
MPC		0.067
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.75
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-60587953;