20-35548585-G-C

Position:

• chr20-35548585-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015966.3(ERGIC3):​c.538G>C​(p.Glu180Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERGIC3 NM_015966.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.87

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]

ERGIC3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERGIC3	NM_015966.3	c.538G>C	p.Glu180Gln	missense_variant	6/13	ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2	c.538G>C	p.Glu180Gln	missense_variant	6/14		NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7	c.538G>C	p.Glu180Gln	missense_variant	6/13	1	NM_015966.3	ENSP00000341358.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 30, 2024

The c.538G>C (p.E180Q) alteration is located in exon 6 (coding exon 6) of the ERGIC3 gene. This alteration results from a G to C substitution at nucleotide position 538, causing the glutamic acid (E) at amino acid position 180 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;.;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N;N;.
REVEL	Benign	0.26
Sift	Uncertain	0.024	D;D;.
Sift4G	Uncertain	0.025	D;D;.
Polyphen		0.99	D;P;.
Vest4		0.71
MutPred		0.32		Gain of MoRF binding (P = 0.0306);Gain of MoRF binding (P = 0.0306);.;
MVP		0.77
MPC		1.3
ClinPred		0.95	D
GERP RS		4.7
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.27
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-34136338;