rs190478555

Positions:

• chr4-183684064-G-A
• chr4-183684064-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000334690.11(TRAPPC11):​c.1287+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,612,732 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (4 hom.)
• Consequence: TRAPPC11 ENST00000334690.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.304

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-183684064-G-A is Benign according to our data. Variant chr4-183684064-G-A is described in ClinVar as [Benign]. Clinvar id is 474345.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-183684064-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6	c.1287+10G>A		intron_variant		ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.1287+10G>A		intron_variant		1	NM_021942.6	ENSP00000335371	P1
TRAPPC11	ENST00000357207.8	c.1287+10G>A		intron_variant		1		ENSP00000349738
TRAPPC11	ENST00000512476.1	c.105+10G>A		intron_variant		1		ENSP00000421004
TRAPPC11	ENST00000505676.5	c.348+58G>A		intron_variant, NMD_transcript_variant		1		ENSP00000422915

Frequencies

GnomAD3 genomes AF: 0.000947 AC: 144 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00131 AC: 328 AN: 251244 Hom.: 0 AF XY: 0.00133 AC XY: 180 AN XY: 135810

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00232

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.00136 AC: 1984 AN: 1460496 Hom.: 4 Cov.: 30 AF XY: 0.00137 AC XY: 999 AN XY: 726666

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.00165

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.000946 AC: 144 AN: 152236 Hom.: 0 Cov.: 33 AF XY: 0.000779 AC XY: 58 AN XY: 74450

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000860 Hom.: 0

Bravo AF: 0.000725

Asia WGS AF: 0.00115 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type R18 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 22, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.36

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: rs190478555; hg19: chr4-184605217;