Variant 5-120686497-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001300783.2(PRR16):c.703A>G(p.Ser235Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PRR16
NM_001300783.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05495149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR16	NM_001300783.2 linkuse as main transcript	c.703A>G	p.Ser235Gly	missense_variant	2/2	ENST00000407149.7	NP_001287712.1	Q569H4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRR16	ENST00000407149.7 linkuse as main transcript	c.703A>G	p.Ser235Gly	missense_variant	2/2	1	NM_001300783.2	ENSP00000385118.2	Q569H4-1
PRR16	ENST00000379551.2 linkuse as main transcript	c.634A>G	p.Ser212Gly	missense_variant	3/3	1		ENSP00000368869.2	Q569H4-3
PRR16	ENST00000446965.2 linkuse as main transcript	c.544A>G	p.Ser182Gly	missense_variant	3/3	1		ENSP00000405491.2	A0A0A0MSW7
PRR16	ENST00000505123.5 linkuse as main transcript	c.493A>G	p.Ser165Gly	missense_variant	4/4	3		ENSP00000423446.1	Q569H4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251234

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 10, 2024

The c.634A>G (p.S212G) alteration is located in exon 3 (coding exon 2) of the PRR16 gene. This alteration results from a A to G substitution at nucleotide position 634, causing the serine (S) at amino acid position 212 to be replaced by a glycine (G). 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

0.061

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.1

DANN

Benign

0.39

DEOGEN2

Benign

0.0016

T;.;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.57

T;T;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.15

N;N;N;.

REVEL

Benign

0.047

Sift

Benign

0.31

T;T;T;.

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0

B;B;.;.

Vest4

0.078

MutPred

0.10

Loss of glycosylation at S235 (P = 0.0335);.;.;.;

MVP

0.10

MPC

0.035

ClinPred

0.070

GERP RS

1.0

Varity_R

0.042

gMVP

0.090

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