16-563785-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_145270.3(PRR35):​c.491C>T​(p.Pro164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000034 in 1,499,084 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

PRR35
NM_145270.3 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.383
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017862111).
BP6
Variant 16-563785-C-T is Benign according to our data. Variant chr16-563785-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3426041.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRR35NM_145270.3 linkc.491C>T p.Pro164Leu missense_variant Exon 2 of 3 ENST00000409413.4 NP_660313.1 P0CG20
PRR35XM_017022959.3 linkc.491C>T p.Pro164Leu missense_variant Exon 2 of 3 XP_016878448.1 P0CG20
PRR35XM_017022960.3 linkc.491C>T p.Pro164Leu missense_variant Exon 3 of 4 XP_016878449.1 P0CG20
PRR35XM_017022961.1 linkc.170+321C>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.491C>T p.Pro164Leu missense_variant Exon 2 of 3 1 NM_145270.3 ENSP00000386499.3 P0CG20

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152144
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000436
AC:
5
AN:
114620
Hom.:
0
AF XY:
0.0000483
AC XY:
3
AN XY:
62088
show subpopulations
Gnomad AFR exome
AF:
0.000130
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000908
Gnomad SAS exome
AF:
0.000202
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000364
AC:
49
AN:
1346940
Hom.:
0
Cov.:
34
AF XY:
0.0000379
AC XY:
25
AN XY:
658916
show subpopulations
Gnomad4 AFR exome
AF:
0.0000654
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000553
Gnomad4 SAS exome
AF:
0.0000832
Gnomad4 FIN exome
AF:
0.0000254
Gnomad4 NFE exome
AF:
0.0000341
Gnomad4 OTH exome
AF:
0.0000180
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152144
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000872
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 10, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.4
DANN
Benign
0.64
DEOGEN2
Benign
0.0064
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.41
N
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.046
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.17
MutPred
0.10
Loss of glycosylation at K163 (P = 0.1254);
MVP
0.055
MPC
0.12
ClinPred
0.0065
T
GERP RS
-2.6
Varity_R
0.036
gMVP
0.12

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: rs758673124; hg19: chr16-613785; COSMIC: COSV99552352; COSMIC: COSV99552352; API