rs200936990

Variant names:

• chr4-183697728-C-G
• rs200936990
• NM_021942.6:c.2744C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-183697728-C-G
• chr4-183697728-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021942.6(TRAPPC11):​c.2744C>G​(p.Thr915Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T915M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAPPC11 NM_021942.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53
• Publications: 0 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2744C>G	p.Thr915Arg	missense	Exon 25 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.2744C>G	p.Thr915Arg	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.2744C>G	p.Thr915Arg	missense	Exon 25 of 30	ENSP00000335371.6	Q7Z392-1
	TRAPPC11	ENST00000357207.8	TSL:1	c.2744C>G	p.Thr915Arg	missense	Exon 25 of 31	ENSP00000349738.4	Q7Z392-3
	TRAPPC11	ENST00000512476.1	TSL:1	c.1562C>G	p.Thr521Arg	missense	Exon 14 of 19	ENSP00000421004.1	D6RHE5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal recessive limb-girdle muscular dystrophy type R18 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.23
Sift	Benign	0.039	D
Sift4G	Uncertain	0.029	D
Polyphen		0.54	P
Vest4		0.88
MutPred		0.49		Gain of helix (P = 0.0861)
MVP		0.60
MPC		0.71
ClinPred		0.83	D
GERP RS		5.5
Varity_R		0.24
gMVP		0.74
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.27		Position offset: 46

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200936990; hg19: chr4-184618881;