NM_021942.6:c.3015G>C

Variant names:

• chr4-183705030-G-C
• rs532244366
• NM_021942.6:c.3015G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_021942.6(TRAPPC11):​c.3015G>C​(p.Pro1005Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000899 in 1,446,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P1005P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: TRAPPC11 NM_021942.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.630
• Publications: 1 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: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P, 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.019).
• BP6: Variant 4-183705030-G-C is Benign according to our data. Variant chr4-183705030-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3730665.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.63 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	NM_021942.6	MANE Select	c.3015G>C	p.Pro1005Pro	synonymous	Exon 27 of 30	NP_068761.4
	TRAPPC11	NM_199053.3		c.3015G>C	p.Pro1005Pro	synonymous	Exon 27 of 31	NP_951008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC11	ENST00000334690.11	TSL:1 MANE Select	c.3015G>C	p.Pro1005Pro	synonymous	Exon 27 of 30	ENSP00000335371.6
	TRAPPC11	ENST00000357207.8	TSL:1	c.3015G>C	p.Pro1005Pro	synonymous	Exon 27 of 31	ENSP00000349738.4
	TRAPPC11	ENST00000512476.1	TSL:1	c.1833G>C	p.Pro611Pro	synonymous	Exon 16 of 19	ENSP00000421004.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251378 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000899 AC: 13 AN: 1446556 Hom.: 0 Cov.: 29 AF XY: 0.00000834 AC XY: 6 AN XY: 719798

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25588

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000950 AC: 8 AN: 84224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52688

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5690

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101240

Other (OTH) AF: 0.00 AC: 0 AN: 59460

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

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
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.63
DANN	Benign	0.70
PhyloP100		-0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs532244366; hg19: chr4-184626183;