Variant chr5-120686671-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001300783.2(PRR16):c.877A>C(p.Lys293Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

PRR16
NM_001300783.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

Variant links:

Genes affected

PRR16 (HGNC:29654): (proline rich 16) Involved in positive regulation of cell size and positive regulation of translation. [provided by Alliance of Genome Resources, Apr 2022]

PRR16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41602457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRR16	NM_001300783.2 linkuse as main transcript	c.877A>C	p.Lys293Gln	missense_variant	2/2	ENST00000407149.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRR16	ENST00000407149.7 linkuse as main transcript	c.877A>C	p.Lys293Gln	missense_variant	2/2	1	NM_001300783.2	P1	Q569H4-1
PRR16	ENST00000379551.2 linkuse as main transcript	c.808A>C	p.Lys270Gln	missense_variant	3/3	1			Q569H4-3
PRR16	ENST00000446965.2 linkuse as main transcript	c.718A>C	p.Lys240Gln	missense_variant	3/3	1
PRR16	ENST00000505123.5 linkuse as main transcript	c.667A>C	p.Lys223Gln	missense_variant	4/4	3			Q569H4-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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 14, 2021

The c.808A>C (p.K270Q) alteration is located in exon 3 (coding exon 2) of the PRR16 gene. This alteration results from a A to C substitution at nucleotide position 808, causing the lysine (K) at amino acid position 270 to be replaced by a glutamine (Q). 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

Pathogenic

0.87

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;.;.;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Benign

0.42

T;T;T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.4

N;D;D;.

REVEL

Benign

0.18

Sift

Uncertain

0.0070

D;D;D;.

Sift4G

Benign

0.23

T;T;T;T

Polyphen

1.0

D;D;.;.

Vest4

0.83

MutPred

0.27

Loss of methylation at K293 (P = 4e-04);.;.;.;

MVP

0.39

MPC

0.26

ClinPred

0.94

GERP RS

5.3

Varity_R

0.38

gMVP

0.47

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