chr4-183664012-G-C

Position:

chr4-183664012-G-C

Variant summary

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

The NM_021942.6(TRAPPC11):c.145G>C(p.Val49Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,613,882 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 12 hom., cov: 31)

Exomes 𝑓: 0.014 ( 221 hom. )

Consequence

TRAPPC11
NM_021942.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 9.60

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]

TRAPPC11 links:

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=0.0064061284).

BP6

Variant 4-183664012-G-C is Benign according to our data. Variant chr4-183664012-G-C is described in ClinVar as [Benign]. Clinvar id is 261442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183664012-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00994 (1513/152204) while in subpopulation SAS AF= 0.0402 (194/4824). AF 95% confidence interval is 0.0356. There are 12 homozygotes in gnomad4. There are 747 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6 linkuse as main transcript	c.145G>C	p.Val49Leu	missense_variant	2/30	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11 linkuse as main transcript	c.145G>C	p.Val49Leu	missense_variant	2/30	1	NM_021942.6	ENSP00000335371	P1	Q7Z392-1

Frequencies

GnomAD3 genomes

AF:

0.00995

AC:

1514

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0402

Gnomad FIN

AF:

0.00858

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0140

AC:

3510

AN:

251478

Hom.:

AF XY:

0.0160

AC XY:

2177

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00543

Gnomad ASJ exome

AF:

0.0185

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.0405

Gnomad FIN exome

AF:

0.00975

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0139

AC:

20268

AN:

1461678

Hom.:

221

Cov.:

AF XY:

0.0149

AC XY:

10832

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00561

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.0407

Gnomad4 FIN exome

AF:

0.00920

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.00994

AC:

1513

AN:

152204

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

747

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.0402

Gnomad4 FIN

AF:

0.00858

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.00869

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0135

AC:

116

ExAC

AF:

0.0143

AC:

1732

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0159

EpiControl

AF:

0.0151

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 27, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 06, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	TRAPPC11: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive limb-girdle muscular dystrophy type R18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0064

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.17

Sift

Benign

0.30

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.47

P;P

Vest4

0.27

MutPred

0.49

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MPC

0.21

ClinPred

0.027

GERP RS

6.0

Varity_R

0.15

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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