Genetic Variant PRP4K:c.2175-4T>G (chr6-4051953-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003913.5(PRP4K):c.2175-4T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 1,529,280 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 11 hom. )

Consequence

PRP4K
NM_003913.5 splice_region, intron

Scores

Splicing: ADA: 0.00006480

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.307

Variant links:

Genes affected

PRP4K (HGNC:17346): (pre-mRNA processing factor kinase PRP4K) Pre-mRNA splicing occurs in two sequential transesterification steps, and the protein encoded by this gene is thought to be involved in pre-mRNA splicing and in signal transduction. This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs). [provided by RefSeq, Jul 2008]

PRP4K links:

FAM217A (HGNC:21362): (family with sequence similarity 217 member A)

FAM217A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 6-4051953-T-G is Benign according to our data. Variant chr6-4051953-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656190.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 399 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRP4K	NM_003913.5 link	c.2175-4T>G		splice_region_variant, intron_variant	Intron 9 of 14	ENST00000337659.11	NP_003904.3	Q13523A0A024QZY5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF4B	ENST00000337659.11 link	c.2175-4T>G		splice_region_variant, intron_variant	Intron 9 of 14	1	NM_003913.5	ENSP00000337194.6		Q13523

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

399

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00257

AC:

525

AN:

203930

Hom.:

AF XY:

0.00256

AC XY:

286

AN XY:

111642

show subpopulations

Gnomad AFR exome

AF:

0.000634

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.000658

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000811

Gnomad FIN exome

AF:

0.000948

Gnomad NFE exome

AF:

0.00412

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00328

AC:

4520

AN:

1377052

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2217

AN XY:

685368

show subpopulations

Gnomad4 AFR exome

AF:

0.000505

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.000591

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000820

Gnomad4 FIN exome

AF:

0.00111

Gnomad4 NFE exome

AF:

0.00382

Gnomad4 OTH exome

AF:

0.00345

GnomAD4 genome

AF:

0.00262

AC:

399

AN:

152228

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.00451

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00347

Hom.:

Bravo

AF:

0.00272

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PRP4K: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.2

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000065

dbscSNV1_RF

Benign

0.0080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over