Genetic Variant NM_003274.5:c.20C>T (chr21-44012513-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003274.5(TRAPPC10):c.20C>T(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00071 in 1,530,952 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 6 hom. )

Consequence

TRAPPC10
NM_003274.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.434

Publications

0 publications found

Variant links:

Genes affected

TRAPPC10 (HGNC:11868): (trafficking protein particle complex subunit 10) The protein encoded by this gene is a transmembrane protein found in the cis-Golgi complex. The encoded protein is part of the multisubunit transport protein particle (TRAPP) complex and may be involved in vesicular transport from the endoplasmic reticulum to the Golgi. Mutations in this gene could be responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy, or for autoimmune polyglandular disease type 1. [provided by RefSeq, Jul 2008]

TRAPPC10 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with microcephaly, short stature, and speech delay
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia

TRAPPC10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004890412).

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003274.5. 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
	TRAPPC10	NM_003274.5	MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 1 of 23	NP_003265.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRAPPC10	ENST00000291574.9	TSL:1 MANE Select	c.20C>T	p.Pro7Leu	missense	Exon 1 of 23	ENSP00000291574.4	P48553-1
TRAPPC10	ENST00000380221.7	TSL:1	c.20C>T	p.Pro7Leu	missense	Exon 1 of 7	ENSP00000369570.3	P48553-2
TRAPPC10	ENST00000422875.5	TSL:1	n.20C>T		non_coding_transcript_exon	Exon 1 of 24	ENSP00000402221.1	F8WE24

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

157

AN:

151476

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000592

Gnomad ASJ

AF:

0.00174

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00610

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00114

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.00105

AC:

144

AN:

137348

AF XY:

0.000983

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000215

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00520

Gnomad NFE exome

AF:

0.000962

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.000674

AC:

930

AN:

1379368

Hom.:

Cov.:

AF XY:

0.000711

AC XY:

484

AN XY:

680558

show subpopulations

African (AFR)

AF:

0.0000333

AC:

AN:

30070

American (AMR)

AF:

0.000230

AC:

AN:

34736

Ashkenazi Jewish (ASJ)

AF:

0.00131

AC:

AN:

24482

East Asian (EAS)

AF:

0.00

AC:

AN:

34626

South Asian (SAS)

AF:

0.00

AC:

AN:

78114

European-Finnish (FIN)

AF:

0.00516

AC:

244

AN:

47284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4082

European-Non Finnish (NFE)

AF:

0.000571

AC:

611

AN:

1069232

Other (OTH)

AF:

0.000599

AC:

AN:

56742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00104

AC:

157

AN:

151584

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41490

American (AMR)

AF:

0.000591

AC:

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.00174

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00610

AC:

AN:

10330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00114

AC:

AN:

67788

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.00113

Hom.:

Bravo

AF:

0.000620

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000560

AC:

ExAC

AF:

0.000252

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.029

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.43

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.98

REVEL

Benign

0.022

Sift

Uncertain

0.023

Sift4G

Benign

0.21

Polyphen

0.015

Vest4

0.16

MVP

0.068

MPC

0.29

ClinPred

0.046

GERP RS

2.7

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.074

gMVP

0.24

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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