9-113275647-C-T

Variant names:

• chr9-113275647-C-T
• rs553952252
• ENST00000374199.9:c.-97C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000374199.9(PRPF4):​c.-97C>T variant causes a 5 prime UTR premature start codon gain change. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRPF4 ENST00000374199.9 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

PRPF4 (HGNC:17349): (pre-mRNA splicing tri-snRNP complex factor PRPF4) The protein encoded by this gene is part of a heteromeric complex that binds U4, U5, and U6 small nuclear RNAs and is involved in pre-mRNA splicing. The encoded protein also is a mitotic checkpoint protein and a regulator of chemoresistance in human ovarian cancer. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2016]

CDC26 (HGNC:17839): (cell division cycle 26) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc26, a component of cell cycle anaphase-promoting complex (APC). APC is composed of a group of highly conserved proteins and functions as a cell cycle-regulated ubiquitin-protein ligase. APC thus is responsible for the cell cycle regulated proteolysis of various proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374199.9. 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
	PRPF4	NM_001244926.2	MANE Select	c.-97C>T		upstream_gene	N/A	NP_001231855.1	O43172-2
	CDC26	NM_139286.4	MANE Select	c.-417G>A		upstream_gene	N/A	NP_644815.1	Q8NHZ8
	PRPF4	NM_004697.5		c.-97C>T		upstream_gene	N/A	NP_004688.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF4	ENST00000374199.9	TSL:1	c.-97C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	ENSP00000363315.4	O43172-1
	PRPF4	ENST00000374199.9	TSL:1	c.-97C>T		5_prime_UTR	Exon 1 of 14	ENSP00000363315.4	O43172-1
	PRPF4	ENST00000374198.5	TSL:1 MANE Select	c.-97C>T		upstream_gene	N/A	ENSP00000363313.4	O43172-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000157 AC: 2 AN: 1271720 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 630802

⚠️ 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: 28550

American (AMR) AF: 0.00 AC: 0 AN: 35500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20808

East Asian (EAS) AF: 0.00 AC: 0 AN: 36058

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5120

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 973620

Other (OTH) AF: 0.00 AC: 0 AN: 53120

⚠️ 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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.98
PhyloP100		3.6
PromoterAI		-0.59	Under-expression

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: rs553952252; hg19: chr9-116037927;