12-29343140-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016570.3(ERGIC2):​c.968G>A​(p.Gly323Glu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ERGIC2
NM_016570.3 missense

Scores

10
8
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51
Variant links:
Genes affected
ERGIC2 (HGNC:30208): (ERGIC and golgi 2) ERGIC2, or PTX1, is a ubiquitously expressed nuclear protein that is downregulated in prostate carcinoma (Kwok et al., 2001 [PubMed 11445006]).[supplied by OMIM, Aug 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ERGIC2NM_016570.3 linkc.968G>A p.Gly323Glu missense_variant Exon 12 of 14 ENST00000360150.9 NP_057654.2 Q96RQ1A0A024RB08Q86TD3
ERGIC2XM_024449009.2 linkc.968G>A p.Gly323Glu missense_variant Exon 12 of 14 XP_024304777.1
ERGIC2XR_001748741.3 linkn.1063G>A non_coding_transcript_exon_variant Exon 12 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERGIC2ENST00000360150.9 linkc.968G>A p.Gly323Glu missense_variant Exon 12 of 14 1 NM_016570.3 ENSP00000353270.4 Q96RQ1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.968G>A (p.G323E) alteration is located in exon 12 (coding exon 11) of the ERGIC2 gene. This alteration results from a G to A substitution at nucleotide position 968, causing the glycine (G) at amino acid position 323 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
1.0
BayesDel_addAF
Pathogenic
0.49
D
BayesDel_noAF
Pathogenic
0.46
CADD
Pathogenic
32
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
D;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.087
D
MetaRNN
Pathogenic
0.94
D;D
MetaSVM
Uncertain
0.45
D
MutationAssessor
Pathogenic
4.3
H;.
PrimateAI
Pathogenic
0.85
D
PROVEAN
Pathogenic
-7.0
D;.
REVEL
Pathogenic
0.89
Sift
Uncertain
0.0010
D;.
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.99
MutPred
0.81
Gain of catalytic residue at S327 (P = 0);.;
MVP
0.80
MPC
0.82
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.91
gMVP
0.98

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: chr12-29496073; API