12-29366947-T-A

Variant names:

• chr12-29366947-T-A
• rs1443477632
• NM_016570.3:c.263A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016570.3(ERGIC2):​c.263A>T​(p.Tyr88Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000663 in 150,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: ERGIC2 NM_016570.3 missense, splice_region
• Scores: Splicing: ADA: 0.01597
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22715291).

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.263A>T	p.Tyr88Phe	missense splice_region	Exon 5 of 14	NP_057654.2	Q96RQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERGIC2	ENST00000360150.9	TSL:1 MANE Select	c.263A>T	p.Tyr88Phe	missense splice_region	Exon 5 of 14	ENSP00000353270.4	Q96RQ1
	ERGIC2	ENST00000966763.1		c.263A>T	p.Tyr88Phe	missense splice_region	Exon 5 of 15	ENSP00000636822.1
	ERGIC2	ENST00000869903.1		c.263A>T	p.Tyr88Phe	missense splice_region	Exon 5 of 14	ENSP00000539962.1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150942 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 27

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150942 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73632

African (AFR) AF: 0.00 AC: 0 AN: 41122

American (AMR) AF: 0.00 AC: 0 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67666

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.20
Eigen_PC	Benign	0.066
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.36	N
PhyloP100		5.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.11
Sift	Benign	0.68	T
Sift4G	Benign	0.66	T
Polyphen		0.0070	B
Vest4		0.40
MutPred		0.50		Gain of catalytic residue at M84 (P = 0)
MVP		0.50
MPC		0.16
ClinPred		0.45	T
GERP RS		5.9
Varity_R		0.11
gMVP		0.25
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.016
dbscSNV1_RF	Benign	0.28
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

Other links and lift over

dbSNP: rs1443477632; hg19: chr12-29519880;