Variant 6-30744422-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003897.4(IER3):c.97C>T(p.Pro33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IER3
NM_003897.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

Variant links:

Genes affected

IER3 (HGNC:5392): (immediate early response 3) This gene functions in the protection of cells from Fas- or tumor necrosis factor type alpha-induced apoptosis. Partially degraded and unspliced transcripts are found after virus infection in vitro, but these transcripts are not found in vivo and do not generate a valid protein. [provided by RefSeq, Jul 2008]

IER3 links:

HCG20 (HGNC:):

HCG20 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34720108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER3	NM_003897.4 linkuse as main transcript	c.97C>T	p.Pro33Ser	missense_variant	1/2	ENST00000259874.6	NP_003888.2	P46695A0A1U9X7X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IER3	ENST00000259874.6 linkuse as main transcript	c.97C>T	p.Pro33Ser	missense_variant	1/2	1	NM_003897.4	ENSP00000259874.5	P46695
IER3	ENST00000376377.2 linkuse as main transcript	c.97C>T	p.Pro33Ser	missense_variant	1/1	6		ENSP00000365557.2	Q5ST79
HCG20	ENST00000656751.1 linkuse as main transcript	n.85+548G>A		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1401988

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.97C>T (p.P33S) alteration is located in exon 1 (coding exon 1) of the IER3 gene. This alteration results from a C to T substitution at nucleotide position 97, causing the proline (P) at amino acid position 33 to be replaced by a serine (S). 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

0.76

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

.;M

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-8.0

D;D

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.47

MutPred

0.34

Gain of phosphorylation at P33 (P = 0.0271);Gain of phosphorylation at P33 (P = 0.0271);

MVP

0.64

MPC

2.1

ClinPred

1.0

GERP RS

4.2

Varity_R

0.63

gMVP

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over