chr16-563586-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145270.3(PRR35):​c.292C>T​(p.Pro98Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PRR35
NM_145270.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.219
Variant links:
Genes affected
PRR35 (HGNC:14139): (proline rich 35)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0853287).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRR35NM_145270.3 linkc.292C>T p.Pro98Ser missense_variant Exon 2 of 3 ENST00000409413.4 NP_660313.1 P0CG20
PRR35XM_017022959.3 linkc.292C>T p.Pro98Ser missense_variant Exon 2 of 3 XP_016878448.1 P0CG20
PRR35XM_017022960.3 linkc.292C>T p.Pro98Ser missense_variant Exon 3 of 4 XP_016878449.1 P0CG20
PRR35XM_017022961.1 linkc.170+122C>T intron_variant Intron 2 of 3 XP_016878450.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRR35ENST00000409413.4 linkc.292C>T p.Pro98Ser missense_variant Exon 2 of 3 1 NM_145270.3 ENSP00000386499.3 P0CG20

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.292C>T (p.P98S) alteration is located in exon 2 (coding exon 1) of the PRR35 gene. This alteration results from a C to T substitution at nucleotide position 292, causing the proline (P) at amino acid position 98 to be replaced by a serine (S). 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
0.079
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
1.4
DANN
Benign
0.65
DEOGEN2
Benign
0.023
T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.085
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.065
Sift
Benign
0.36
T
Sift4G
Benign
0.079
T
Polyphen
0.64
P
Vest4
0.14
MutPred
0.14
Gain of phosphorylation at P98 (P = 0.0099);
MVP
0.085
MPC
0.12
ClinPred
0.14
T
GERP RS
3.9
Varity_R
0.031
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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.

Other links and lift over

dbSNP: rs2035478876; hg19: chr16-613586; API