rs62617790

Variant names:

• chr4-183697783-G-C
• rs62617790
• NM_021942.6:c.2799G>C
• TRAPPC11 p.Gln933His

Your query was ambiguous. Multiple possible variants found:

• chr4-183697783-G-C
• chr4-183697783-G-A
• chr4-183697783-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021942.6(TRAPPC11):​c.2799G>C​(p.Gln933His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,613,842 control chromosomes in the GnomAD database, including 14,189 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1047 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13142 hom.)
• Consequence: TRAPPC11 NM_021942.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.68
• Publications: 20 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type R18

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Myriad Women's Health, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P
• intellectual disability-hyperkinetic movement-truncal ataxia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• triple-A syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017220974).
• BP6: Variant 4-183697783-G-C is Benign according to our data. Variant chr4-183697783-G-C is described in ClinVar as Benign. ClinVar VariationId is 261451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021942.6. 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
	TRAPPC11	NM_021942.6	MANE Select	c.2799G>C	p.Gln933His	missense	Exon 25 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.2799G>C	p.Gln933His	missense	Exon 25 of 31	NP_951008.1	Q7Z392-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.2799G>C	p.Gln933His	missense	Exon 25 of 30	ENSP00000335371.6	Q7Z392-1
	TRAPPC11	ENST00000357207.8	TSL:1	c.2799G>C	p.Gln933His	missense	Exon 25 of 31	ENSP00000349738.4	Q7Z392-3
	TRAPPC11	ENST00000512476.1	TSL:1	c.1617G>C	p.Gln539His	missense	Exon 14 of 19	ENSP00000421004.1	D6RHE5

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15921 AN: 152002 Hom.: 1048 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.119

GnomAD2 exomes AF: 0.133 AC: 33364 AN: 251266 AF XY: 0.141

Gnomad AFR exome AF: 0.0473

Gnomad AMR exome AF: 0.0518

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.237

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.126 AC: 184724 AN: 1461722 Hom.: 13142 Cov.: 33 AF XY: 0.131 AC XY: 94910 AN XY: 727172

African (AFR) AF: 0.0476 AC: 1592 AN: 33474

American (AMR) AF: 0.0547 AC: 2448 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4453 AN: 26134

East Asian (EAS) AF: 0.270 AC: 10736 AN: 39700

South Asian (SAS) AF: 0.232 AC: 19968 AN: 86252

European-Finnish (FIN) AF: 0.125 AC: 6660 AN: 53412

Middle Eastern (MID) AF: 0.147 AC: 834 AN: 5692

European-Non Finnish (NFE) AF: 0.117 AC: 130136 AN: 1111958

Other (OTH) AF: 0.131 AC: 7897 AN: 60376

GnomAD4 genome AF: 0.105 AC: 15920 AN: 152120 Hom.: 1047 Cov.: 32 AF XY: 0.109 AC XY: 8114 AN XY: 74356

African (AFR) AF: 0.0495 AC: 2055 AN: 41510

American (AMR) AF: 0.0779 AC: 1190 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1193 AN: 5160

South Asian (SAS) AF: 0.229 AC: 1108 AN: 4830

European-Finnish (FIN) AF: 0.125 AC: 1317 AN: 10568

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8067 AN: 67996

Other (OTH) AF: 0.119 AC: 251 AN: 2108

Alfa AF: 0.124 Hom.: 954

Bravo AF: 0.0966

Asia WGS AF: 0.212 AC: 736 AN: 3478

EpiCase AF: 0.122

EpiControl AF: 0.127

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type R18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.7
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.14
Sift	Uncertain	0.025	D
Sift4G	Benign	0.11	T
Varity_R		0.21
gMVP		0.51
Mutation Taster		=96/4	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs62617790;

hg19: chr4-184618936;

COSMIC: COSV58215418;

COSMIC: COSV58215418;