Variant chr7-100155084-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000316937.8(TRAPPC14):c.1670A>C(p.Asp557Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000188 in 1,613,656 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TRAPPC14
ENST00000316937.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

Variant links:

Genes affected

TRAPPC14 (HGNC:25604): (trafficking protein particle complex subunit 14) Enables alpha-tubulin binding activity. Involved in cilium assembly and regulation of cell population proliferation. Located in several cellular components, including microtubule cytoskeleton; midbody; and plasma membrane. Part of TRAPPII protein complex. Implicated in primary autosomal recessive microcephaly. [provided by Alliance of Genome Resources, Apr 2022]

TRAPPC14 links:

LAMTOR4 (HGNC:33772): (late endosomal/lysosomal adaptor, MAPK and MTOR activator 4) Contributes to guanyl-nucleotide exchange factor activity and molecular adaptor activity. Involved in several processes, including cellular response to amino acid stimulus; positive regulation of TOR signaling; and protein localization to lysosome. Located in lysosome. Part of Ragulator complex. [provided by Alliance of Genome Resources, Apr 2022]

LAMTOR4 links:

TRAPPC14 (HGNC:):

TRAPPC14 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23228401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC14	NM_018275.5 linkuse as main transcript	c.1670A>C	p.Asp557Ala	missense_variant	11/11	ENST00000316937.8	NP_060745.3	Q8WVR3-1
TRAPPC14	NM_001303470.2 linkuse as main transcript	c.863A>C	p.Asp288Ala	missense_variant	11/11		NP_001290399.1	B3KNS5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC14	ENST00000316937.8 linkuse as main transcript	c.1670A>C	p.Asp557Ala	missense_variant	11/11	1	NM_018275.5	ENSP00000324741.3		Q8WVR3-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151928

Hom.:

Cov.:

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251230

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000205

AC:

300

AN:

1461728

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

140

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000266

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74226

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:

0.0000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Microcephaly 25, primary, autosomal recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Sep 30, 2019

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

.;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.55

.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Uncertain

-2.5

D;D;.

REVEL

Benign

0.15

Sift

Benign

0.045

D;T;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.93

.;P;.

Vest4

0.29

MutPred

0.29

.;Loss of solvent accessibility (P = 0.0169);.;

MVP

0.65

MPC

0.76

ClinPred

0.30

GERP RS

4.7

Varity_R

0.20

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over