rs79804817

Positions:

• chr4-183705034-G-A
• chr4-183705034-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_021942.6(TRAPPC11):​c.3019G>A​(p.Val1007Met) variant causes a missense change. The variant allele was found at a frequency of 0.00168 in 1,598,108 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (51 hom.)
• Consequence: TRAPPC11 NM_021942.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 6.22

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0064311624).
• BP6: Variant 4-183705034-G-A is Benign according to our data. Variant chr4-183705034-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-183705034-G-A is described in Lovd as [Benign]. Variant chr4-183705034-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0021 (320/152236) while in subpopulation EAS AF= 0.0424 (219/5168). AF 95% confidence interval is 0.0378. There are 6 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC11	NM_021942.6	c.3019G>A	p.Val1007Met	missense_variant	27/30	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.3019G>A	p.Val1007Met	missense_variant	27/30	1	NM_021942.6	ENSP00000335371.6

Frequencies

GnomAD3 genomes AF: 0.00211 AC: 321 AN: 152118 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00427 AC: 1073 AN: 251382 Hom.: 27 AF XY: 0.00378 AC XY: 513 AN XY: 135846

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.0494

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.00370

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00163 AC: 2361 AN: 1445872 Hom.: 51 Cov.: 29 AF XY: 0.00163 AC XY: 1174 AN XY: 719436

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.0000896

Gnomad4 ASJ exome AF: 0.00234

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.000975

Gnomad4 FIN exome AF: 0.00310

Gnomad4 NFE exome AF: 0.0000972

Gnomad4 OTH exome AF: 0.00231

GnomAD4 genome AF: 0.00210 AC: 320 AN: 152236 Hom.: 6 Cov.: 32 AF XY: 0.00242 AC XY: 180 AN XY: 74436

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00175 Hom.: 12

Bravo AF: 0.00192

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00387 AC: 470

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 09, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T;.;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;D
MetaRNN	Benign	0.0064	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.2	M;M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.95	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.018	D;D;D
Sift4G	Uncertain	0.032	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.73
MVP		0.46
MPC		0.71
ClinPred		0.028	T
GERP RS		4.9
Varity_R		0.12
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79804817; hg19: chr4-184626187; COSMIC: COSV58215427; COSMIC: COSV58215427;