6-4056999-C-T

Variant names:

• chr6-4056999-C-T
• rs853407
• NM_003913.5:c.2582-37C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003913.5(PRP4K):​c.2582-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,498,174 control chromosomes in the GnomAD database, including 355,294 homozygotes. 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: 𝑓 0.71 (38195 hom., cov: 32)
  • Exomes 𝑓: 0.69 (317099 hom.)
• Consequence: PRP4K NM_003913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRP4K	NM_003913.5	c.2582-37C>T		intron_variant	Intron 12 of 14	ENST00000337659.11	NP_003904.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF4B	ENST00000337659.11	c.2582-37C>T		intron_variant	Intron 12 of 14	1	NM_003913.5	ENSP00000337194.6

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107581 AN: 151984 Hom.: 38156 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.704

GnomAD3 exomes AF: 0.701 AC: 140552 AN: 200630 Hom.: 49409 AF XY: 0.694 AC XY: 75959 AN XY: 109394

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.739

Gnomad ASJ exome AF: 0.675

Gnomad EAS exome AF: 0.770

Gnomad SAS exome AF: 0.674

Gnomad FIN exome AF: 0.686

Gnomad NFE exome AF: 0.685

Gnomad OTH exome AF: 0.693

GnomAD4 exome AF: 0.686 AC: 923298 AN: 1346072 Hom.: 317099 Cov.: 26 AF XY: 0.685 AC XY: 458120 AN XY: 668754

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.788

Gnomad4 SAS exome AF: 0.674

Gnomad4 FIN exome AF: 0.696

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.689

GnomAD4 genome AF: 0.708 AC: 107682 AN: 152102 Hom.: 38195 Cov.: 32 AF XY: 0.707 AC XY: 52575 AN XY: 74332

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.682

Gnomad4 OTH AF: 0.705

Alfa AF: 0.684 Hom.: 17689

Bravo AF: 0.712

Asia WGS AF: 0.752 AC: 2616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.42

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: rs853407; hg19: chr6-4057233; COSMIC: COSV61784562; COSMIC: COSV61784562;