chr14-45095350-C-A

Position:

• chr14-45095350-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017922.4(PRPF39):​c.111C>A​(p.Asn37Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)
• Consequence: PRPF39 NM_017922.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.120

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08951023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF39	NM_017922.4	c.111C>A	p.Asn37Lys	missense_variant	2/14	ENST00000355765.11	NP_060392.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF39	ENST00000355765.11	c.111C>A	p.Asn37Lys	missense_variant	2/14	1	NM_017922.4	ENSP00000348010.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Sep 24, 2024

The c.111C>A (p.N37K) alteration is located in exon 2 (coding exon 1) of the PRPF39 gene. This alteration results from a C to A substitution at nucleotide position 111, causing the asparagine (N) at amino acid position 37 to be replaced by a lysine (K). 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	0.23
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0057	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.090	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.025
Sift	Benign	0.038	D;D
Sift4G	Benign	0.85	T;T
Polyphen		0.26	B;.
Vest4		0.29
MutPred		0.29		Gain of ubiquitination at N37 (P = 0.0018);Gain of ubiquitination at N37 (P = 0.0018);
MVP		0.27
MPC		0.57
ClinPred		0.12	T
GERP RS		3.6
Varity_R		0.063
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr14-45564553;