14-45110749-C-T

Position:

• chr14-45110749-C-T

Variant summary

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

The NM_017922.4(PRPF39):​c.1504C>T​(p.Leu502Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPF39 NM_017922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.95

Genes affected

PRPF39 (HGNC:20314): (pre-mRNA processing factor 39) Predicted to be involved in mRNA 5'-splice site recognition. Predicted to be part of U1 snRNP; U2-type prespliceosome; and commitment complex. [provided by Alliance of Genome Resources, Apr 2022]

PRPF39 (HGNC:):

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/exons	MANE	Protein	UniProt
PRPF39	NM_017922.4	c.1504C>T	p.Leu502Phe	missense_variant	10/14	ENST00000355765.11	NP_060392.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF39	ENST00000355765.11	c.1504C>T	p.Leu502Phe	missense_variant	10/14	1	NM_017922.4	ENSP00000348010.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.1504C>T (p.L502F) alteration is located in exon 10 (coding exon 9) of the PRPF39 gene. This alteration results from a C to T substitution at nucleotide position 1504, causing the leucine (L) at amino acid position 502 to be replaced by a phenylalanine (F). 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	Benign	0.11
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.055	T
Polyphen		0.99	D
Vest4		0.57
MutPred		0.40		Gain of methylation at K497 (P = 0.0688);
MVP		0.29
MPC		0.54
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.18
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1566699030; hg19: chr14-45579952;