12-49325801-C-T

Variant summary

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

The NM_005480.4(TROAP):​c.550C>T​(p.Pro184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

TROAP
NM_005480.4 missense

Scores

2
3
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.942
Variant links:
Genes affected
TROAP (HGNC:12327): (trophinin associated protein) Predicted to be involved in cell adhesion. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.0050569475).
BP6
Variant 12-49325801-C-T is Benign according to our data. Variant chr12-49325801-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 722962.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TROAPNM_005480.4 linkc.550C>T p.Pro184Ser missense_variant Exon 5 of 15 ENST00000257909.8 NP_005471.3 Q12815-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TROAPENST00000257909.8 linkc.550C>T p.Pro184Ser missense_variant Exon 5 of 15 1 NM_005480.4 ENSP00000257909.3 Q12815-1

Frequencies

GnomAD3 genomes
AF:
0.00176
AC:
268
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00625
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.0000147
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000510
AC:
128
AN:
251022
Hom.:
0
AF XY:
0.000354
AC XY:
48
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.00710
Gnomad AMR exome
AF:
0.000318
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000200
AC:
293
AN:
1461814
Hom.:
0
Cov.:
32
AF XY:
0.000162
AC XY:
118
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.00741
Gnomad4 AMR exome
AF:
0.000335
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.000381
GnomAD4 genome
AF:
0.00176
AC:
268
AN:
152292
Hom.:
0
Cov.:
32
AF XY:
0.00153
AC XY:
114
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00623
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000371
Hom.:
1
Bravo
AF:
0.00229
ESP6500AA
AF:
0.00522
AC:
23
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000692
AC:
84

ClinVar

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

Submissions by phenotype

not provided Benign:1
Feb 20, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;.;T;T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.085
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.69
T;T;T;T
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.0051
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
.;.;M;.
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-4.5
D;D;D;D
REVEL
Benign
0.11
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.029
D;T;T;D
Polyphen
0.34
B;.;B;.
Vest4
0.70
MVP
0.30
MPC
0.71
ClinPred
0.075
T
GERP RS
3.1
Varity_R
0.54
gMVP
0.094

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs140223921; hg19: chr12-49719584; API