11-60900616-T-C

Position:

• chr11-60900616-T-C

Variant summary

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

The NM_014502.5(PRPF19):​c.794A>G​(p.Lys265Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,404,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRPF19 NM_014502.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.48

Genes affected

PRPF19 (HGNC:17896): (pre-mRNA processing factor 19) Enables identical protein binding activity and ubiquitin-ubiquitin ligase activity. Involved in several processes, including DNA damage checkpoint signaling; cellular protein metabolic process; and mRNA splicing, via spliceosome. Acts upstream of or within protein polyubiquitination. Located in cytoplasm; nuclear speck; and site of double-strand break. Part of Prp19 complex and U2-type catalytic step 2 spliceosome. Colocalizes with DNA replication factor A complex. [provided by Alliance of Genome Resources, Apr 2022]

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
PRPF19	NM_014502.5	c.794A>G	p.Lys265Arg	missense_variant	10/16	ENST00000227524.9	NP_055317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF19	ENST00000227524.9	c.794A>G	p.Lys265Arg	missense_variant	10/16	1	NM_014502.5	ENSP00000227524.4
PRPF19	ENST00000541371.5	c.718+238A>G		intron_variant		3		ENSP00000440266.1
PRPF19	ENST00000540473.5	c.114+694A>G		intron_variant		5		ENSP00000443031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1404630 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 693206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Non-immune hydrops fetalis Uncertain:1

Uncertain significance, no assertion criteria provided

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Apr 29, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.25	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.28
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.019	D
Polyphen		0.96	D
Vest4		0.61
MutPred		0.53		Loss of disorder (P = 0.08);
MVP		0.60
MPC		2.0
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.65
gMVP		0.25

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: chr11-60668088;