chr14-45102531-C-T

Variant names:

• chr14-45102531-C-T
• NM_017922.4:c.572C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017922.4(PRPF39):​c.572C>T​(p.Thr191Ile) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPF39 NM_017922.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30250552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017922.4. 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
	PRPF39	NM_017922.4	MANE Select	c.572C>T	p.Thr191Ile	missense splice_region	Exon 5 of 14	NP_060392.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF39	ENST00000355765.11	TSL:1 MANE Select	c.572C>T	p.Thr191Ile	missense splice_region	Exon 5 of 14	ENSP00000348010.6	Q86UA1-1
	PRPF39	ENST00000931178.1		c.572C>T	p.Thr191Ile	missense splice_region	Exon 5 of 14	ENSP00000601237.1
	PRPF39	ENST00000905876.1		c.572C>T	p.Thr191Ile	missense splice_region	Exon 5 of 14	ENSP00000575935.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.086
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.44	N
PhyloP100		6.2
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.14
Sift	Benign	0.35	T
Sift4G	Benign	0.40	T
Polyphen		0.010	B
Vest4		0.55
MutPred		0.37		Gain of catalytic residue at A195 (P = 0.0032)
MVP		0.29
MPC		0.50
ClinPred		0.46	T
GERP RS		5.6
Varity_R		0.11
gMVP		0.35
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

hg19: chr14-45571734;