19-57365022-T-C

Position:

• chr19-57365022-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001355204.2(TRAPPC2B):​c.189T>C​(p.Thr63Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00701 in 1,612,350 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (46 hom.)
• Consequence: TRAPPC2B NM_001355204.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.215

Genes affected

TRAPPC2B (HGNC:10710): (trafficking protein particle complex subunit 2B) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Located in endoplasmic reticulum and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF547 (HGNC:26432): (zinc finger protein 547) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268133 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 19-57365022-T-C is Benign according to our data. Variant chr19-57365022-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650570.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.215 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAPPC2B	NM_001355204.2	c.189T>C	p.Thr63Thr	synonymous_variant	2/2	ENST00000543226.2	NP_001342133.1
ZNF547	NM_173631.4	c.-13+1319T>C		intron_variant		ENST00000282282.4	NP_775902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAPPC2B	ENST00000543226.2	c.189T>C	p.Thr63Thr	synonymous_variant	2/2	1	NM_001355204.2	ENSP00000442778.1
ZNF547	ENST00000282282.4	c.-13+1319T>C		intron_variant		1	NM_173631.4	ENSP00000282282.3
ENSG00000268133	ENST00000597658.1	c.-13+1319T>C		intron_variant		3		ENSP00000472894.1

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 942 AN: 152194 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00413

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00614 AC: 1521 AN: 247904 Hom.: 12 AF XY: 0.00606 AC XY: 816 AN XY: 134548

Gnomad AFR exome AF: 0.000786

Gnomad AMR exome AF: 0.00492

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.0000559

Gnomad SAS exome AF: 0.00571

Gnomad FIN exome AF: 0.00414

Gnomad NFE exome AF: 0.00770

Gnomad OTH exome AF: 0.00813

GnomAD4 exome AF: 0.00710 AC: 10366 AN: 1460038 Hom.: 46 Cov.: 31 AF XY: 0.00727 AC XY: 5279 AN XY: 726382

Gnomad4 AFR exome AF: 0.000807

Gnomad4 AMR exome AF: 0.00504

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00539

Gnomad4 FIN exome AF: 0.00470

Gnomad4 NFE exome AF: 0.00761

Gnomad4 OTH exome AF: 0.00855

GnomAD4 genome AF: 0.00619 AC: 943 AN: 152312 Hom.: 7 Cov.: 32 AF XY: 0.00619 AC XY: 461 AN XY: 74494

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.00785

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00653 Hom.: 0

Bravo AF: 0.00609

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

TRAPPC2B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs184372842; hg19: chr19-57876390;