19-54115599-G-A

Position:

• chr19-54115599-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_013342.4(TFPT):​c.-330C>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 0.000969 in 474,728 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: TFPT NM_013342.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.121

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFPT	NM_013342.4	c.-330C>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.-330C>T		5_prime_UTR_variant	1/6	1	NM_013342.4	ENSP00000375639	P1
PRPF31	ENST00000419967.5	c.-207G>A		5_prime_UTR_variant	1/13	5		ENSP00000405166

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 121 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00105 AC: 339 AN: 322374 Hom.: 2 Cov.: 0 AF XY: 0.00105 AC XY: 175 AN XY: 167278

Gnomad4 AFR exome AF: 0.000203

Gnomad4 AMR exome AF: 0.000438

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00248

Gnomad4 FIN exome AF: 0.000600

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.000961

GnomAD4 genome AF: 0.000794 AC: 121 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.000792 AC XY: 59 AN XY: 74508

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00139 Hom.: 0

Bravo AF: 0.000816

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Retinitis Pigmentosa, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs587674748; hg19: chr19-54618979;