17-59193609-C-T

Variant names:

• chr17-59193609-C-T
• NM_018304.4:c.520C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018304.4(PRR11):​c.520C>T​(p.Pro174Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR11 NM_018304.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.976

Genes affected

PRR11 (HGNC:25619): (proline rich 11) Involved in regulation of cell cycle. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088285595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR11	NM_018304.4	c.520C>T	p.Pro174Ser	missense_variant	Exon 5 of 10	ENST00000262293.9	NP_060774.2
PRR11	XM_024450828.2	c.520C>T	p.Pro174Ser	missense_variant	Exon 6 of 11		XP_024306596.1
PRR11	XM_047436387.1	c.520C>T	p.Pro174Ser	missense_variant	Exon 6 of 11		XP_047292343.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR11	ENST00000262293.9	c.520C>T	p.Pro174Ser	missense_variant	Exon 5 of 10	1	NM_018304.4	ENSP00000262293.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.520C>T (p.P174S) alteration is located in exon 5 (coding exon 4) of the PRR11 gene. This alteration results from a C to T substitution at nucleotide position 520, causing the proline (P) at amino acid position 174 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Benign	0.086	T;T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.48	.;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.088	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.4	D;.;.
REVEL	Benign	0.030
Sift	Benign	0.21	T;.;.
Sift4G	Benign	0.082	T;T;T
Polyphen		0.060	B;.;B
Vest4		0.18
MutPred		0.13		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.24
MPC		0.24
ClinPred		0.079	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-57270970;