chr11-60900604-C-T

Position:

• chr11-60900604-C-T

Variant summary

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

The NM_014502.5(PRPF19):​c.806G>A​(p.Ser269Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPF19 NM_014502.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78

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.806G>A	p.Ser269Asn	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.806G>A	p.Ser269Asn	missense_variant	10/16	1	NM_014502.5	ENSP00000227524.4
PRPF19	ENST00000541371.5	c.718+250G>A		intron_variant		3		ENSP00000440266.1
PRPF19	ENST00000540473.5	c.114+706G>A		intron_variant		5		ENSP00000443031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.806G>A (p.S269N) alteration is located in exon 10 (coding exon 10) of the PRPF19 gene. This alteration results from a G to A substitution at nucleotide position 806, causing the serine (S) at amino acid position 269 to be replaced by an asparagine (N). 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	0.13
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.24
Sift	Benign	0.19	T
Sift4G	Benign	0.48	T
Polyphen		0.0090	B
Vest4		0.77
MutPred		0.78		Loss of disorder (P = 0.0888);
MVP		0.51
MPC		1.1
ClinPred		0.63	D
GERP RS		5.6
Varity_R		0.48
gMVP		0.58

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: chr11-60668076;