rs150593522

Variant names:

• chr4-183694726-AT-A
• rs150593522
• NM_021942.6:c.2628+10delT

Your query was ambiguous. Multiple possible variants found:

• chr4-183694726-AT-A
• chr4-183694726-AT-ATT

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The ENST00000334690.11(TRAPPC11):​c.2628+4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,603,446 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: TRAPPC11 ENST00000334690.11 splice_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.713

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 4-183694726-AT-A is Benign according to our data. Variant chr4-183694726-AT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 474351.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr4-183694726-AT-A is described in Lovd as [Benign]. Variant chr4-183694726-AT-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00112 (1622/1451268) while in subpopulation NFE AF= 0.00142 (1576/1109624). AF 95% confidence interval is 0.00136. There are 0 homozygotes in gnomad4_exome. There are 759 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRAPPC11	NM_021942.6	c.2628+10delT		intron_variant	Intron 23 of 29	ENST00000334690.11	NP_068761.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRAPPC11	ENST00000334690.11	c.2628+4delT		splice_region_variant, intron_variant	Intron 23 of 29	1	NM_021942.6	ENSP00000335371.6
TRAPPC11	ENST00000357207.8	c.2628+4delT		splice_region_variant, intron_variant	Intron 23 of 30	1		ENSP00000349738.4
TRAPPC11	ENST00000512476.1	c.1446+4delT		splice_region_variant, intron_variant	Intron 12 of 18	1		ENSP00000421004.1
TRAPPC11	ENST00000505676.5	n.*742+4delT		splice_region_variant, intron_variant	Intron 11 of 18	1		ENSP00000422915.1

Frequencies

GnomAD3 genomes AF: 0.000480 AC: 73 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000453 AC: 108 AN: 238294 Hom.: 0 AF XY: 0.000427 AC XY: 55 AN XY: 128876

Gnomad AFR exome AF: 0.000193

Gnomad AMR exome AF: 0.0000652

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000924

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.00112 AC: 1622 AN: 1451268 Hom.: 0 Cov.: 30 AF XY: 0.00105 AC XY: 759 AN XY: 721564

Gnomad4 AFR exome AF: 0.000184

Gnomad4 AMR exome AF: 0.0000725

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000241

Gnomad4 FIN exome AF: 0.0000750

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.000500

GnomAD4 genome AF: 0.000480 AC: 73 AN: 152178 Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74418

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000927

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000111 Hom.: 1

Bravo AF: 0.000423

EpiCase AF: 0.000875

EpiControl AF: 0.000954

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Jul 01, 2017

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:1

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs150593522; hg19: chr4-184615879;