Variant 22-31703698-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173566.3(PRR14L):c.5852T>G(p.Leu1951Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,597,706 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

PRR14L
NM_173566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

Variant links:

Genes affected

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

PRR14L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR14L	NM_173566.3 linkuse as main transcript	c.5852T>G	p.Leu1951Trp	missense_variant	6/9	ENST00000327423.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR14L	ENST00000327423.11 linkuse as main transcript	c.5852T>G	p.Leu1951Trp	missense_variant	6/9	5	NM_173566.3	P1	Q5THK1-1
PRR14L	ENST00000330495.8 linkuse as main transcript	c.761T>G	p.Leu254Trp	missense_variant	3/6	1
PRR14L	ENST00000431684.1 linkuse as main transcript	c.1859T>G	p.Leu620Trp	missense_variant, NMD_transcript_variant	3/5	2
PRR14L	ENST00000432485.1 linkuse as main transcript	c.23T>G	p.Leu8Trp	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000170

AC:

AN:

235772

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1445504

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

717992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.0000696

Gnomad4 ASJ exome

AF:

0.0000399

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000725

Gnomad4 OTH exome

AF:

0.0000503

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.5852T>G (p.L1951W) alteration is located in exon 6 (coding exon 5) of the PRR14L gene. This alteration results from a T to G substitution at nucleotide position 5852, causing the leucine (L) at amino acid position 1951 to be replaced by a tryptophan (W). 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

0.32

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.12

Cadd

Pathogenic

Dann

Benign

0.96

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.79

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.70

MutPred

0.40

Gain of catalytic residue at A1950 (P = 0.0148);

MVP

0.082

MPC

0.51

ClinPred

0.82

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over