rs79804817

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000334690.11(TRAPPC11):​c.3019G>A​(p.Val1007Met) variant causes a missense change. The variant allele was found at a frequency of 0.00168 in 1,598,108 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 51 hom. )

Consequence

TRAPPC11
ENST00000334690.11 missense

Scores

2
8
8

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.22
Variant links:
Genes affected
TRAPPC11 (HGNC:25751): (trafficking protein particle complex subunit 11) The protein encoded by this gene is a subunit of the TRAPP (transport protein particle) tethering complex, which functions in intracellular vesicle trafficking. This subunit is involved in early stage endoplasmic reticulum-to-Golgi vesicle transport. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0064311624).
BP6
Variant 4-183705034-G-A is Benign according to our data. Variant chr4-183705034-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183705034-G-A is described in Lovd as [Benign]. Variant chr4-183705034-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0021 (320/152236) while in subpopulation EAS AF= 0.0424 (219/5168). AF 95% confidence interval is 0.0378. There are 6 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRAPPC11NM_021942.6 linkuse as main transcriptc.3019G>A p.Val1007Met missense_variant 27/30 ENST00000334690.11 NP_068761.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRAPPC11ENST00000334690.11 linkuse as main transcriptc.3019G>A p.Val1007Met missense_variant 27/301 NM_021942.6 ENSP00000335371 P1Q7Z392-1

Frequencies

GnomAD3 genomes
AF:
0.00211
AC:
321
AN:
152118
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.0423
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.00377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000368
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00427
AC:
1073
AN:
251382
Hom.:
27
AF XY:
0.00378
AC XY:
513
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00248
Gnomad EAS exome
AF:
0.0494
Gnomad SAS exome
AF:
0.000653
Gnomad FIN exome
AF:
0.00370
Gnomad NFE exome
AF:
0.000194
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00163
AC:
2361
AN:
1445872
Hom.:
51
Cov.:
29
AF XY:
0.00163
AC XY:
1174
AN XY:
719436
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.0000896
Gnomad4 ASJ exome
AF:
0.00234
Gnomad4 EAS exome
AF:
0.0455
Gnomad4 SAS exome
AF:
0.000975
Gnomad4 FIN exome
AF:
0.00310
Gnomad4 NFE exome
AF:
0.0000972
Gnomad4 OTH exome
AF:
0.00231
GnomAD4 genome
AF:
0.00210
AC:
320
AN:
152236
Hom.:
6
Cov.:
32
AF XY:
0.00242
AC XY:
180
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.0424
Gnomad4 SAS
AF:
0.00269
Gnomad4 FIN
AF:
0.00377
Gnomad4 NFE
AF:
0.000368
Gnomad4 OTH
AF:
0.00190
Alfa
AF:
0.00175
Hom.:
12
Bravo
AF:
0.00192
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00387
AC:
470
Asia WGS
AF:
0.0240
AC:
85
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxFeb 09, 2019- -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Autosomal recessive limb-girdle muscular dystrophy type R18 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.030
T;.;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D
MetaRNN
Benign
0.0064
T;T;T
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.2
M;M;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-0.95
N;N;N
REVEL
Benign
0.25
Sift
Uncertain
0.018
D;D;D
Sift4G
Uncertain
0.032
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.73
MVP
0.46
MPC
0.71
ClinPred
0.028
T
GERP RS
4.9
Varity_R
0.12
gMVP
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs79804817; hg19: chr4-184626187; COSMIC: COSV58215427; COSMIC: COSV58215427; API