12-29368259-C-A

Variant names:

• chr12-29368259-C-A
• NM_016570.3:c.244G>T

Variant summary

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

The NM_016570.3(ERGIC2):​c.244G>T​(p.Val82Phe) 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: ERGIC2 NM_016570.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.36

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]

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 rank	MANE	Protein	UniProt
ERGIC2	NM_016570.3	c.244G>T	p.Val82Phe	missense_variant	Exon 4 of 14	ENST00000360150.9	NP_057654.2
ERGIC2	XM_024449009.2	c.244G>T	p.Val82Phe	missense_variant	Exon 4 of 14		XP_024304777.1
ERGIC2	XR_001748741.3	n.339G>T		non_coding_transcript_exon_variant	Exon 4 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERGIC2	ENST00000360150.9	c.244G>T	p.Val82Phe	missense_variant	Exon 4 of 14	1	NM_016570.3	ENSP00000353270.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.244G>T (p.V82F) alteration is located in exon 4 (coding exon 3) of the ERGIC2 gene. This alteration results from a G to T substitution at nucleotide position 244, causing the valine (V) at amino acid position 82 to be replaced by a phenylalanine (F). 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	0.93
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T;.;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.0068	T
MetaRNN	Uncertain	0.74	D;D;D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L;.;.;.;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.2	D;.;D;D;D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D;.;D;D;D;D
Sift4G	Benign	0.24	T;T;D;.;.;.
Polyphen		0.86	P;.;.;.;.;.
Vest4		0.85
MutPred		0.70		Gain of catalytic residue at M84 (P = 0);.;Gain of catalytic residue at M84 (P = 0);Gain of catalytic residue at M84 (P = 0);.;Gain of catalytic residue at M84 (P = 0);
MVP		0.46
MPC		0.71
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-29521192;