rs200658266

Positions:

• chr4-183664088-G-A
• chr4-183664088-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_021942.6(TRAPPC11):​c.204+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,598,710 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0028 (9 hom.)
• Consequence: TRAPPC11 NM_021942.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.400

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-183664088-G-A is Benign according to our data. Variant chr4-183664088-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRAPPC11	NM_021942.6	c.204+17G>A		intron_variant		ENST00000334690.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.204+17G>A		intron_variant		1	NM_021942.6	P1

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 262 AN: 151950 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00291

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.00160 AC: 399 AN: 249608 Hom.: 1 AF XY: 0.00172 AC XY: 232 AN XY: 135088

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000980

Gnomad FIN exome AF: 0.000802

Gnomad NFE exome AF: 0.00258

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00275 AC: 3982 AN: 1446642 Hom.: 9 Cov.: 27 AF XY: 0.00272 AC XY: 1961 AN XY: 720514

Gnomad4 AFR exome AF: 0.000572

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.00361

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000814

Gnomad4 FIN exome AF: 0.000970

Gnomad4 NFE exome AF: 0.00324

Gnomad4 OTH exome AF: 0.00279

GnomAD4 genome AF: 0.00172 AC: 262 AN: 152068 Hom.: 1 Cov.: 31 AF XY: 0.00164 AC XY: 122 AN XY: 74314

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.0000947

Gnomad4 NFE AF: 0.00291

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.00255 Hom.: 0

Bravo AF: 0.00160

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely 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

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.93
DANN	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs200658266; hg19: chr4-184585241;