20-35542154-C-G

Variant names:

• chr20-35542154-C-G
• rs1344361931
• NM_015966.3:c.57C>G

Variant summary

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

The NM_015966.3(ERGIC3):​c.57C>G​(p.Asp19Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ERGIC3 NM_015966.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERGIC3	NM_015966.3	c.57C>G	p.Asp19Glu	missense_variant	Exon 1 of 13	ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2	c.57C>G	p.Asp19Glu	missense_variant	Exon 1 of 14		NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7	c.57C>G	p.Asp19Glu	missense_variant	Exon 1 of 13	1	NM_015966.3	ENSP00000341358.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.57C>G (p.D19E) alteration is located in exon 1 (coding exon 1) of the ERGIC3 gene. This alteration results from a C to G substitution at nucleotide position 57, causing the aspartic acid (D) at amino acid position 19 to be replaced by a glutamic acid (E). 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	Pathogenic	0.96
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.23
Sift	Benign	0.056	T;T;T
Sift4G	Benign	0.095	T;T;D
Polyphen		1.0	D;D;.
Vest4		0.69
MutPred		0.61		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP		0.78
MPC		1.4
ClinPred		0.83	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.97

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: rs1344361931; hg19: chr20-34129903;