20-35557024-G-T

Position:

• chr20-35557024-G-T

Variant summary

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

The NM_015966.3(ERGIC3):​c.931G>T​(p.Gly311Trp) variant causes a missense change involving the alteration of a 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: 8.18

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/exons	MANE	Protein	UniProt
ERGIC3	NM_015966.3	c.931G>T	p.Gly311Trp	missense_variant	11/13	ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2	c.946G>T	p.Gly316Trp	missense_variant	12/14		NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7	c.931G>T	p.Gly311Trp	missense_variant	11/13	1	NM_015966.3	ENSP00000341358	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

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

Feb 02, 2024

The c.946G>T (p.G316W) alteration is located in exon 12 (coding exon 12) of the ERGIC3 gene. This alteration results from a G to T substitution at nucleotide position 946, causing the glycine (G) at amino acid position 316 to be replaced by a tryptophan (W). 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	0.87
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Pathogenic	3.1	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-2.2	N;N;.
REVEL	Benign	0.27
Sift	Uncertain	0.0090	D;D;.
Sift4G	Uncertain	0.028	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.67
MVP		0.71
MPC		1.4
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1045225363; hg19: chr20-34144795;