19-54115619-C-A

Position:

• chr19-54115619-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_013342.4(TFPT):​c.-350G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 428,626 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (5 hom.)
• Consequence: TFPT NM_013342.4 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.648

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 19-54115619-C-A is Benign according to our data. Variant chr19-54115619-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 330087.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPT	NM_013342.4	c.-350G>T		5_prime_UTR_variant	1/6	ENST00000391759.6	NP_037474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFPT	ENST00000391759.6	c.-350G>T		5_prime_UTR_variant	1/6	1	NM_013342.4	ENSP00000375639	P1
PRPF31	ENST00000419967.5	c.-187C>A		5_prime_UTR_variant	1/13	5		ENSP00000405166

Frequencies

GnomAD3 genomes AF: 0.00447 AC: 681 AN: 152244 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00701

Gnomad OTH AF: 0.00430

GnomAD4 exome AF: 0.00490 AC: 1354 AN: 276264 Hom.: 5 Cov.: 0 AF XY: 0.00491 AC XY: 697 AN XY: 142032

Gnomad4 AFR exome AF: 0.000901

Gnomad4 AMR exome AF: 0.00251

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.00126

Gnomad4 NFE exome AF: 0.00689

Gnomad4 OTH exome AF: 0.00460

GnomAD4 genome AF: 0.00448 AC: 682 AN: 152362 Hom.: 2 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74516

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00703

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00492 Hom.: 0

Bravo AF: 0.00414

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Retinitis Pigmentosa, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

PRPF31: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.8
DANN	Benign	0.57

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: rs45619231; hg19: chr19-54618999;