Genetic Variant TROAP:p.Pro184Ser (chr12-49325801-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_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

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.942

Publications

2 publications found

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]

TROAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

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 VariationId is 722962.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005480.4. 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
	TROAP	NM_005480.4	MANE Select	c.550C>T	p.Pro184Ser	missense	Exon 5 of 15	NP_005471.3
	TROAP	NM_001410976.1		c.550C>T	p.Pro184Ser	missense	Exon 5 of 14	NP_001397905.1	F8W130

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TROAP	ENST00000257909.8	TSL:1 MANE Select	c.550C>T	p.Pro184Ser	missense	Exon 5 of 15	ENSP00000257909.3	Q12815-1
TROAP	ENST00000546735.5	TSL:1	n.*195C>T		non_coding_transcript_exon	Exon 4 of 10	ENSP00000447876.1	F8VR46
TROAP	ENST00000546735.5	TSL:1	n.*195C>T		3_prime_UTR	Exon 4 of 10	ENSP00000447876.1	F8VR46

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152174

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000510

AC:

128

AN:

251022

AF XY:

0.000354

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 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.:

Cov.:

AF XY:

0.000162

AC XY:

118

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.00741

AC:

248

AN:

33478

American (AMR)

AF:

0.000335

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111996

Other (OTH)

AF:

0.000381

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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

AF:

0.00176

AC:

268

AN:

152292

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00623

AC:

259

AN:

41546

American (AMR)

AF:

0.000196

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000572

Hom.:

Bravo

AF:

0.00229

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000692

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.69

M_CAP

Benign

0.0093

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

0.94

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.029

Polyphen

0.34

Vest4

0.70

MVP

0.30

MPC

0.71

ClinPred

0.075

GERP RS

3.1

Varity_R

0.54

gMVP

0.094

Mutation Taster

=83/17

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over