Genetic Variant PRR14L:p.Leu1395Phe (chr22-31713654-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_173566.3(PRR14L):c.4185G>C(p.Leu1395Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,551,944 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0010 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 25 hom. )

Consequence

PRR14L
NM_173566.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.215

Publications

5 publications found

Variant links:

Genes affected

PRR14L (HGNC:28738): (proline rich 14 like)

PRR14L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004124522).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00101 (153/152220) while in subpopulation EAS AF = 0.0256 (133/5186). AF 95% confidence interval is 0.0221. There are 3 homozygotes in GnomAd4. There are 86 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRR14L	NM_173566.3 link	c.4185G>C	p.Leu1395Phe	missense_variant	Exon 4 of 9	ENST00000327423.11	NP_775837.2	Q5THK1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRR14L	ENST00000327423.11 link	c.4185G>C	p.Leu1395Phe	missense_variant	Exon 4 of 9	5	NM_173566.3	ENSP00000331845.6		Q5THK1-1
PRR14L	ENST00000431684.1 link	n.192G>C		non_coding_transcript_exon_variant	Exon 1 of 5	2		ENSP00000389527.1		H7BZH1

Frequencies

GnomAD3 genomes

AF:

0.000999

AC:

152

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00152

AC:

239

AN:

157744

AF XY:

0.00157

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00176

Gnomad EAS exome

AF:

0.0176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.00202

GnomAD4 exome

AF:

0.00100

AC:

1405

AN:

1399724

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

718

AN XY:

690346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31600

American (AMR)

AF:

0.0000840

AC:

AN:

35708

Ashkenazi Jewish (ASJ)

AF:

0.00159

AC:

AN:

25182

East Asian (EAS)

AF:

0.0322

AC:

1151

AN:

35738

South Asian (SAS)

AF:

0.000883

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49404

Middle Eastern (MID)

AF:

0.000526

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000853

AC:

AN:

1079042

Other (OTH)

AF:

0.000792

AC:

AN:

58114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00101

AC:

153

AN:

152220

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41526

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.0256

AC:

133

AN:

5186

South Asian (SAS)

AF:

0.00104

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

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

Genome Het

Genome 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

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.00104

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000629

AC:

ExAC

AF:

0.00106

AC:

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PhyloP100

0.21

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.7

REVEL

Benign

0.038

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.022

Polyphen

0.082

Vest4

0.046

MutPred

0.073

Loss of disorder (P = 0.1357);

MVP

0.068

MPC

0.073

ClinPred

0.013

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

gMVP

0.042

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over