Genetic Variant NM_018304.4:c.316C>T (chr17-59185476-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018304.4(PRR11):c.316C>T(p.Arg106Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000807 in 1,573,894 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

PRR11
NM_018304.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.360

Publications

3 publications found

Variant links:

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]

PRR11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10079056).

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.316C>T	p.Arg106Cys	missense	Exon 4 of 10	NP_060774.2	D2SNZ4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRR11	ENST00000262293.9	TSL:1 MANE Select	c.316C>T	p.Arg106Cys	missense	Exon 4 of 10	ENSP00000262293.5	Q96HE9
PRR11	ENST00000614081.1	TSL:1	c.316C>T	p.Arg106Cys	missense	Exon 4 of 11	ENSP00000481852.1	Q96HE9
PRR11	ENST00000580177.5	TSL:1	n.316C>T		non_coding_transcript_exon	Exon 4 of 11	ENSP00000463733.1	Q96HE9

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

136552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000827

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000727

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000102

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000484

Gnomad OTH

AF:

0.000552

GnomAD2 exomes

AF:

0.000129

AC:

AN:

247324

AF XY:

0.000134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000821

AC:

118

AN:

1437342

Hom.:

Cov.:

AF XY:

0.0000741

AC XY:

AN XY:

715590

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32782

American (AMR)

AF:

0.000165

AC:

AN:

42446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25588

East Asian (EAS)

AF:

0.00

AC:

AN:

38996

South Asian (SAS)

AF:

0.0000957

AC:

AN:

83616

European-Finnish (FIN)

AF:

0.0000378

AC:

AN:

52938

Middle Eastern (MID)

AF:

0.000531

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.0000794

AC:

AN:

1096192

Other (OTH)

AF:

0.000118

AC:

AN:

59130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000659

AC:

AN:

136552

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

66660

show subpopulations

African (AFR)

AF:

0.0000827

AC:

AN:

36296

American (AMR)

AF:

0.0000727

AC:

AN:

13746

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3112

East Asian (EAS)

AF:

0.00

AC:

AN:

4532

South Asian (SAS)

AF:

0.00

AC:

AN:

4114

European-Finnish (FIN)

AF:

0.000102

AC:

AN:

9776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000484

AC:

AN:

62046

Other (OTH)

AF:

0.000552

AC:

AN:

1812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000277

Hom.:

ExAC

AF:

0.000214

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.15

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.79

M_CAP

Benign

0.0024

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.36

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.089

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0070

Polyphen

0.055

Vest4

0.35

MutPred

0.48

Gain of sheet (P = 0.1208)

MVP

0.31

MPC

0.27

ClinPred

0.25

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.27

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over