20-35556221-C-T

Position:

• chr20-35556221-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000348547.7(ERGIC3):​c.829C>T​(p.Gln277Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERGIC3 ENST00000348547.7 stop_gained
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.37

Genes affected

ERGIC3 (HGNC:15927): (ERGIC and golgi 3) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport and retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-35556221-C-T is Pathogenic according to our data. Variant chr20-35556221-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2661907.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERGIC3	NM_015966.3	c.829C>T	p.Gln277Ter	stop_gained	10/13	ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2	c.844C>T	p.Gln282Ter	stop_gained	11/14		NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7	c.829C>T	p.Gln277Ter	stop_gained	10/13	1	NM_015966.3	ENSP00000341358	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Developmental disorder Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Clinical Genetics Laboratory, University Hospital Schleswig-Holstein

Sep 19, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.66
CADD	Pathogenic	50
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
MutationTaster	Benign	1.0	A;A;A;A
Vest4		0.53
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-34143992;