20-35548618-A-G

Position:

• chr20-35548618-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015966.3(ERGIC3):​c.571A>G​(p.Met191Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERGIC3 NM_015966.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.19

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32487357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERGIC3	NM_015966.3	c.571A>G	p.Met191Val	missense_variant	6/13	ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2	c.571A>G	p.Met191Val	missense_variant	6/14		NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7	c.571A>G	p.Met191Val	missense_variant	6/13	1	NM_015966.3	ENSP00000341358	P4

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

Feb 28, 2023

The c.571A>G (p.M191V) alteration is located in exon 6 (coding exon 6) of the ERGIC3 gene. This alteration results from a A to G substitution at nucleotide position 571, causing the methionine (M) at amino acid position 191 to be replaced by a valine (V). 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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.020	T;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	0.013
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.92	L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.59	N;N;.
REVEL	Benign	0.29
Sift	Benign	0.80	T;T;.
Sift4G	Benign	0.55	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.71
MutPred		0.46		Gain of methylation at K190 (P = 0.0502);Gain of methylation at K190 (P = 0.0502);.;
MVP		0.50
MPC		0.55
ClinPred		0.54	D
GERP RS		4.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
Varity_R		0.19
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-34136371;