20-35547447-G-C

Position:

• chr20-35547447-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015966.3(ERGIC3):​c.403G>C​(p.Asp135His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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: 1.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18295968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERGIC3	NM_015966.3	c.403G>C	p.Asp135His	missense_variant	5/13	ENST00000348547.7	NP_057050.1
ERGIC3	NM_198398.2	c.403G>C	p.Asp135His	missense_variant	5/14		NP_938408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERGIC3	ENST00000348547.7	c.403G>C	p.Asp135His	missense_variant	5/13	1	NM_015966.3	ENSP00000341358	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Apr 15, 2024

The c.403G>C (p.D135H) alteration is located in exon 5 (coding exon 5) of the ERGIC3 gene. This alteration results from a G to C substitution at nucleotide position 403, causing the aspartic acid (D) at amino acid position 135 to be replaced by a histidine (H). 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	0.092
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N
MutationTaster	Benign	0.94	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.021
Sift	Benign	0.10	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.21	B;B
Vest4		0.33
MutPred		0.30		Loss of solvent accessibility (P = 0.0217);Loss of solvent accessibility (P = 0.0217);
MVP		0.49
MPC		0.65
ClinPred		0.33	T
GERP RS		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.052
gMVP		0.47

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: chr20-34135198;