11-65619914-T-C

Variant names:

• chr11-65619914-T-C
• NM_032223.4:c.1990T>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032223.4(PCNX3):​c.1990T>C​(p.Tyr664His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCNX3 NM_032223.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19

Genes affected

PCNX3 (HGNC:18760): (pecanex 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX3	NM_032223.4	c.1990T>C	p.Tyr664His	missense_variant	Exon 8 of 35	ENST00000355703.4	NP_115599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX3	ENST00000355703.4	c.1990T>C	p.Tyr664His	missense_variant	Exon 8 of 35	5	NM_032223.4	ENSP00000347931.3
PCNX3	ENST00000531045.1	n.57T>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1990T>C (p.Y664H) alteration is located in exon 8 (coding exon 8) of the PCNX3 gene. This alteration results from a T to C substitution at nucleotide position 1990, causing the tyrosine (Y) at amino acid position 664 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.16
Sift	Benign	0.10	T
Sift4G	Benign	0.48	T
Polyphen		1.0	D
Vest4		0.87
MutPred		0.38		Gain of disorder (P = 0.0299);
MVP		0.60
ClinPred		0.82	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.089
gMVP		0.53

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: chr11-65387385;