rs757493239

Variant names:

• chr10-13600289-C-T
• rs757493239
• NM_003675.4:c.190C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003675.4(PRPF18):​c.190C>T​(p.Pro64Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,460,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: PRPF18 NM_003675.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71
• Publications: 0 publications found

Genes affected

PRPF18 (HGNC:17351): (pre-mRNA processing factor 18) Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to the yeast splicing factor Prp18. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18476304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003675.4. 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
	PRPF18	NM_003675.4	MANE Select	c.190C>T	p.Pro64Ser	missense	Exon 3 of 10	NP_003666.1	Q99633-1
	PRPF18	NM_001395875.1		c.217C>T	p.Pro73Ser	missense	Exon 4 of 11	NP_001382804.1
	PRPF18	NM_001395876.1		c.172C>T	p.Pro58Ser	missense	Exon 5 of 12	NP_001382805.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF18	ENST00000378572.8	TSL:1 MANE Select	c.190C>T	p.Pro64Ser	missense	Exon 3 of 10	ENSP00000367835.3	Q99633-1
	PRPF18	ENST00000937338.1		c.190C>T	p.Pro64Ser	missense	Exon 3 of 11	ENSP00000607397.1
	PRPF18	ENST00000855616.1		c.217C>T	p.Pro73Ser	missense	Exon 4 of 11	ENSP00000525675.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249948 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1460138 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 726418

African (AFR) AF: 0.00 AC: 0 AN: 33270

American (AMR) AF: 0.00 AC: 0 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39496

South Asian (SAS) AF: 0.00 AC: 0 AN: 86080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111192

Other (OTH) AF: 0.0000663 AC: 4 AN: 60324

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000548

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

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	0.19
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.00012
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.26	N
REVEL	Benign	0.14
Sift	Benign	0.74	T
Sift4G	Benign	0.70	T
Polyphen		0.067	B
Vest4		0.48
MVP		0.65
MPC		0.81
ClinPred		0.47	T
GERP RS		6.1
Varity_R		0.094
gMVP		0.53
Mutation Taster		=29/71	disease causing

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

Other links and lift over

dbSNP: rs757493239; hg19: chr10-13642289;