Genetic Variant PRR35:p.Thr82Arg (chr16-563539-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145270.3(PRR35):c.245C>G(p.Thr82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,458,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T82M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PRR35
NM_145270.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

Publications

0 publications found

Variant links:

Genes affected

PRR35 (HGNC:14139): (proline rich 35)

PRR35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.116855055).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145270.3. 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
	PRR35	NM_145270.3	MANE Select	c.245C>G	p.Thr82Arg	missense	Exon 2 of 3	NP_660313.1	P0CG20

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRR35	ENST00000409413.4	TSL:1 MANE Select	c.245C>G	p.Thr82Arg	missense	Exon 2 of 3	ENSP00000386499.3	P0CG20
PRR35	ENST00000870054.1		c.245C>G	p.Thr82Arg	missense	Exon 2 of 3	ENSP00000540113.1
PRR35	ENST00000870055.1		c.245C>G	p.Thr82Arg	missense	Exon 3 of 4	ENSP00000540114.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244566

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000548

AC:

AN:

1458822

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.0000224

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111208

Other (OTH)

AF:

0.0000166

AC:

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000830

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

-0.30

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.5

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.024

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.42

M_CAP

Benign

0.028

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.4

PROVEAN

Benign

-1.5

REVEL

Benign

0.029

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.060

Polyphen

0.68

Vest4

0.17

MutPred

0.17

Loss of glycosylation at T82 (P = 0.0021)

MVP

0.040

MPC

0.51

ClinPred

0.12

GERP RS

1.7

Varity_R

0.089

gMVP

0.16

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over