16-563683-C-T

Variant summary

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

The NM_145270.3(PRR35):​c.389C>T​(p.Pro130Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000153 in 1,565,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PRR35
NM_145270.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
Variant links:
Genes affected
PRR35 (HGNC:14139): (proline rich 35)

Genome browser will be placed here

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=0.06201142).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRR35NM_145270.3 linkc.389C>T p.Pro130Leu missense_variant Exon 2 of 3 ENST00000409413.4 NP_660313.1 P0CG20
PRR35XM_017022959.3 linkc.389C>T p.Pro130Leu missense_variant Exon 2 of 3 XP_016878448.1 P0CG20
PRR35XM_017022960.3 linkc.389C>T p.Pro130Leu missense_variant Exon 3 of 4 XP_016878449.1 P0CG20
PRR35XM_017022961.1 linkc.170+219C>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.389C>T p.Pro130Leu missense_variant Exon 2 of 3 1 NM_145270.3 ENSP00000386499.3 P0CG20

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
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
GnomAD3 exomes
AF:
0.0000238
AC:
4
AN:
167886
Hom.:
0
AF XY:
0.0000431
AC XY:
4
AN XY:
92776
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000737
Gnomad SAS exome
AF:
0.000122
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000163
AC:
23
AN:
1413334
Hom.:
0
Cov.:
33
AF XY:
0.0000243
AC XY:
17
AN XY:
700170
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000106
Gnomad4 SAS exome
AF:
0.0000861
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.14e-7
Gnomad4 OTH exome
AF:
0.000187
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.0000172
AC:
2
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 11, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.389C>T (p.P130L) 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 389, causing the proline (P) at amino acid position 130 to be replaced by a leucine (L). 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
0.10
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
12
DANN
Benign
0.74
DEOGEN2
Benign
0.056
T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.062
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.019
Sift
Benign
0.064
T
Sift4G
Benign
0.37
T
Polyphen
0.043
B
Vest4
0.20
MVP
0.095
MPC
0.13
ClinPred
0.19
T
GERP RS
1.5
Varity_R
0.043
gMVP
0.15

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.

Other links and lift over

dbSNP: rs370093259; hg19: chr16-613683; API