19-54115693-G-A

Variant names:

• chr19-54115693-G-A
• rs17526361
• ENST00000419967.5:c.-113G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000419967.5(PRPF31):​c.-113G>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 0.00000561 in 178,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: PRPF31 ENST00000419967.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.-113G>A		upstream_gene	N/A	NP_056444.3
	TFPT	NM_013342.4	MANE Select	c.-424C>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.-113G>A		5_prime_UTR	Exon 1 of 13	ENSP00000405166.2	Q8WWY3-4
	PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.-113G>A		upstream_gene	N/A	ENSP00000324122.4	Q8WWY3-1
	TFPT	ENST00000391759.6	TSL:1 MANE Select	c.-424C>T		upstream_gene	N/A	ENSP00000375639.1	P0C1Z6-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000561 AC: 1 AN: 178288 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 89502

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 6696

American (AMR) AF: 0.00 AC: 0 AN: 6632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7358

East Asian (EAS) AF: 0.0000663 AC: 1 AN: 15094

South Asian (SAS) AF: 0.00 AC: 0 AN: 16356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 107854

Other (OTH) AF: 0.00 AC: 0 AN: 11830

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.1
DANN	Benign	0.83
PhyloP100		0.59
PromoterAI		-0.066	Neutral

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: rs17526361; hg19: chr19-54619073;