Genetic Variant NM_016570.3:c.814G>A (chr12-29345454-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PP3_ModerateBP6

The NM_016570.3(ERGIC2):c.814G>A(p.Val272Met) 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 Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ERGIC2
NM_016570.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.69

Publications

0 publications found

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]

ERGIC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

BP6

Variant 12-29345454-C-T is Benign according to our data. Variant chr12-29345454-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2681261.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016570.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERGIC2	NM_016570.3	MANE Select	c.814G>A	p.Val272Met	missense	Exon 11 of 14	NP_057654.2	Q96RQ1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERGIC2	ENST00000360150.9	TSL:1 MANE Select	c.814G>A	p.Val272Met	missense	Exon 11 of 14	ENSP00000353270.4	Q96RQ1
ERGIC2	ENST00000966763.1		c.937G>A	p.Val313Met	missense	Exon 12 of 15	ENSP00000636822.1
ERGIC2	ENST00000869903.1		c.814G>A	p.Val272Met	missense	Exon 11 of 14	ENSP00000539962.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1425810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711518

African (AFR)

AF:

0.00

AC:

AN:

32528

American (AMR)

AF:

0.00

AC:

AN:

44152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25842

East Asian (EAS)

AF:

0.00

AC:

AN:

39360

South Asian (SAS)

AF:

0.00

AC:

AN:

84820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082776

Other (OTH)

AF:

0.00

AC:

AN:

59226

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

-0.14

MutationAssessor

Pathogenic

3.0

PhyloP100

7.7

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.4

REVEL

Pathogenic

0.69

Sift

Benign

0.039

Sift4G

Uncertain

0.038

Polyphen

1.0

Vest4

0.78

MutPred

0.78

Gain of catalytic residue at Q269 (P = 0.0014)

MVP

0.78

MPC

0.71

ClinPred

0.98

GERP RS

6.0

Varity_R

0.25

gMVP

0.94

Mutation Taster

=19/81

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over