14-60121235-A-C

Variant names:

• chr14-60121235-A-C
• rs150511705
• NM_001330177.2:c.1982A>C

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330177.2. 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
	PCNX4	NM_001330177.2	MANE Select	c.1982A>C	p.Gln661Pro	missense	Exon 8 of 11	NP_001317106.1	Q63HM2
	PCNX4	NM_022495.5		c.1280A>C	p.Gln427Pro	missense	Exon 7 of 10	NP_071940.4	Q63HM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX4	ENST00000406854.6	TSL:5 MANE Select	c.1982A>C	p.Gln661Pro	missense	Exon 8 of 11	ENSP00000384801.1	Q63HM2
	PCNX4	ENST00000868338.1		c.1934A>C	p.Gln645Pro	missense	Exon 8 of 11	ENSP00000538397.1
	PCNX4	ENST00000868337.1		c.1562A>C	p.Gln521Pro	missense	Exon 8 of 11	ENSP00000538396.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33220

American (AMR) AF: 0.00 AC: 0 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 39306

South Asian (SAS) AF: 0.00 AC: 0 AN: 86044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108006

Other (OTH) AF: 0.0000167 AC: 1 AN: 59924

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		8.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.039	D
Polyphen		0.95	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
Mutation Taster		=51/49	polymorphism

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: rs150511705; hg19: chr14-60587953;