17-59185514-G-C

Variant names:

• chr17-59185514-G-C
• NM_018304.4:c.354G>C

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.354G>C​(p.Gln118His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRR11 NM_018304.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.878
• 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=0.17490456).

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.354G>C	p.Gln118His	missense	Exon 4 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.354G>C	p.Gln118His	missense	Exon 4 of 10	ENSP00000262293.5	Q96HE9
	PRR11	ENST00000614081.1	TSL:1	c.354G>C	p.Gln118His	missense	Exon 4 of 11	ENSP00000481852.1	Q96HE9
	PRR11	ENST00000580177.5	TSL:1	n.354G>C		non_coding_transcript_exon	Exon 4 of 11	ENSP00000463733.1	Q96HE9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459920 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726366

African (AFR) AF: 0.00 AC: 0 AN: 33294

American (AMR) AF: 0.00 AC: 0 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111378

Other (OTH) AF: 0.00 AC: 0 AN: 60288

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.88
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.11
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.030	D
Polyphen		0.91	P
Vest4		0.30
MutPred		0.20		Gain of catalytic residue at Q118 (P = 0.0688)
MVP		0.50
MPC		0.56
ClinPred		0.90	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.094
gMVP		0.27
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr17-57262875; COSMIC: COSV51874779; COSMIC: COSV51874779;