17-59193681-C-T

Variant names:

• chr17-59193681-C-T
• rs149181181
• NM_018304.4:c.592C>T

Variant summary

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

The NM_018304.4(PRR11):​c.592C>T​(p.Pro198Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P198A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRR11 NM_018304.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.551
• Publications: 0 publications found

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

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 (MetaRNN=0.07629883).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018304.4. 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
	PRR11	NM_018304.4	MANE Select	c.592C>T	p.Pro198Ser	missense	Exon 5 of 10	NP_060774.2	D2SNZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRR11	ENST00000262293.9	TSL:1 MANE Select	c.592C>T	p.Pro198Ser	missense	Exon 5 of 10	ENSP00000262293.5	Q96HE9
	PRR11	ENST00000614081.1	TSL:1	c.592C>T	p.Pro198Ser	missense	Exon 5 of 11	ENSP00000481852.1	Q96HE9
	PRR11	ENST00000580177.5	TSL:1	n.592C>T		non_coding_transcript_exon	Exon 5 of 11	ENSP00000463733.1	Q96HE9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.57
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.55
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.067
Sift	Benign	0.27	T
Sift4G	Benign	0.073	T
Polyphen		0.42	B
Vest4		0.36
MutPred		0.19		Loss of loop (P = 0.0031)
MVP		0.30
MPC		0.27
ClinPred		0.27	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.24

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: rs149181181; hg19: chr17-57271042;