rs62358032

Positions:

• chr4-183693964-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021942.6(TRAPPC11):​c.2434A>C​(p.Thr812Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,613,816 control chromosomes in the GnomAD database, including 10,653 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (572 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10081 hom.)
• Consequence: TRAPPC11 NM_021942.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.465

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014404655).
• BP6: Variant 4-183693964-A-C is Benign according to our data. Variant chr4-183693964-A-C is described in ClinVar as [Benign]. Clinvar id is 261448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183693964-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6	c.2434A>C	p.Thr812Pro	missense_variant	22/30	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.2434A>C	p.Thr812Pro	missense_variant	22/30	1	NM_021942.6	ENSP00000335371.6

Frequencies

GnomAD3 genomes AF: 0.0744 AC: 11324 AN: 152148 Hom.: 573 Cov.: 33

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0511

GnomAD3 exomes AF: 0.0811 AC: 20383 AN: 251280 Hom.: 1098 AF XY: 0.0837 AC XY: 11360 AN XY: 135800

Gnomad AFR exome AF: 0.0197

Gnomad AMR exome AF: 0.0322

Gnomad ASJ exome AF: 0.0469

Gnomad EAS exome AF: 0.0268

Gnomad SAS exome AF: 0.0748

Gnomad FIN exome AF: 0.0958

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.0812

GnomAD4 exome AF: 0.111 AC: 162478 AN: 1461550 Hom.: 10081 Cov.: 32 AF XY: 0.110 AC XY: 79923 AN XY: 727062

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.0477

Gnomad4 EAS exome AF: 0.0392

Gnomad4 SAS exome AF: 0.0737

Gnomad4 FIN exome AF: 0.0984

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.0908

GnomAD4 genome AF: 0.0744 AC: 11327 AN: 152266 Hom.: 572 Cov.: 33 AF XY: 0.0717 AC XY: 5340 AN XY: 74458

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.0304

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.106 Hom.: 743

Bravo AF: 0.0672

TwinsUK AF: 0.132 AC: 489

ALSPAC AF: 0.128 AC: 493

ESP6500AA AF: 0.0227 AC: 100

ESP6500EA AF: 0.116 AC: 997

ExAC AF: 0.0828 AC: 10056

Asia WGS AF: 0.0400 AC: 138 AN: 3478

EpiCase AF: 0.104

EpiControl AF: 0.101

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
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

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.7
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.80	T;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.59	N;N;N
REVEL	Benign	0.015
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.13
MPC		0.24
ClinPred		0.0017	T
GERP RS		-1.6
Varity_R		0.060
gMVP		0.55

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

Other links and lift over

dbSNP: rs62358032; hg19: chr4-184615117;