rs587601857

Variant names:

• chr19-54115679-G-A
• rs587601857
• ENST00000419967.5:c.-127G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-54115679-G-A
• chr19-54115679-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The ENST00000419967.5(PRPF31):​c.-127G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 346,250 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: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: PRPF31 ENST00000419967.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.335
• Publications: 0 publications found

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]

TFPT (HGNC:13630): (TCF3 fusion partner) Predicted to enable DNA binding activity and protein kinase binding activity. Involved in apoptotic signaling pathway. Located in nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000722 (11/152322) while in subpopulation SAS AF = 0.00207 (10/4826). AF 95% confidence interval is 0.00112. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000419967.5. 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
	PRPF31	NM_015629.4	MANE Select	c.-127G>A		upstream_gene	N/A	NP_056444.3
	TFPT	NM_013342.4	MANE Select	c.-410C>T		upstream_gene	N/A	NP_037474.1	P0C1Z6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF31	ENST00000419967.5	TSL:5	c.-127G>A		5_prime_UTR	Exon 1 of 13	ENSP00000405166.2	Q8WWY3-4
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.-127G>A		upstream_gene	N/A	ENSP00000324122.4	Q8WWY3-1
	TFPT	ENST00000391759.6	TSL:1 MANE Select	c.-410C>T		upstream_gene	N/A	ENSP00000375639.1	P0C1Z6-1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 25 AN: 193928 Hom.: 0 Cov.: 0 AF XY: 0.000235 AC XY: 23 AN XY: 97718

African (AFR) AF: 0.00 AC: 0 AN: 7216

American (AMR) AF: 0.00 AC: 0 AN: 7108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7776

East Asian (EAS) AF: 0.00 AC: 0 AN: 16014

South Asian (SAS) AF: 0.00127 AC: 22 AN: 17368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 874

European-Non Finnish (NFE) AF: 0.0000255 AC: 3 AN: 117602

Other (OTH) AF: 0.00 AC: 0 AN: 12752

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.90
PhyloP100		-0.34
PromoterAI		0.19	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs587601857; hg19: chr19-54619059;