19-54121847-C-T

Variant names:

• chr19-54121847-C-T
• rs113691122
• NM_015629.4:c.239-13C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015629.4(PRPF31):​c.239-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,604,744 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (126 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (122 hom.)
• Consequence: PRPF31 NM_015629.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.476

Genes affected

PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]

PRPF31-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-54121847-C-T is Benign according to our data. Variant chr19-54121847-C-T is described in ClinVar as [Benign]. Clinvar id is 330096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.239-13C>T		intron_variant	Intron 3 of 13	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.239-13C>T		intron_variant	Intron 3 of 13		XP_006723200.1
PRPF31	XM_047438587.1	c.239-13C>T		intron_variant	Intron 3 of 9		XP_047294543.1
PRPF31-AS1	NR_186329.1	n.564G>A		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.239-13C>T		intron_variant	Intron 3 of 13	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3395 AN: 152224 Hom.: 127 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00975

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.00572 AC: 1338 AN: 233922 Hom.: 49 AF XY: 0.00427 AC XY: 541 AN XY: 126756

Gnomad AFR exome AF: 0.0808

Gnomad AMR exome AF: 0.00388

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000171

Gnomad SAS exome AF: 0.000104

Gnomad FIN exome AF: 0.0000515

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.00208

GnomAD4 exome AF: 0.00221 AC: 3209 AN: 1452402 Hom.: 122 Cov.: 32 AF XY: 0.00191 AC XY: 1376 AN XY: 721674

Gnomad4 AFR exome AF: 0.0793

Gnomad4 AMR exome AF: 0.00452

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000763

Gnomad4 SAS exome AF: 0.0000946

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000659

Gnomad4 OTH exome AF: 0.00455

GnomAD4 genome AF: 0.0223 AC: 3397 AN: 152342 Hom.: 126 Cov.: 32 AF XY: 0.0219 AC XY: 1634 AN XY: 74498

Gnomad4 AFR AF: 0.0769

Gnomad4 AMR AF: 0.00967

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0117 Hom.: 12

Bravo AF: 0.0260

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.5
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs113691122; hg19: chr19-54625226; COSMIC: COSV58087473; COSMIC: COSV58087473;