6-30744482-T-G

Position:

• chr6-30744482-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003897.4(IER3):​c.37A>C​(p.Ile13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IER3 NM_003897.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.219

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]

HCG20 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071365565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER3	NM_003897.4	c.37A>C	p.Ile13Leu	missense_variant	1/2	ENST00000259874.6	NP_003888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER3	ENST00000259874.6	c.37A>C	p.Ile13Leu	missense_variant	1/2	1	NM_003897.4	ENSP00000259874.5
IER3	ENST00000376377.2	c.37A>C	p.Ile13Leu	missense_variant	1/1	6		ENSP00000365557.2
HCG20	ENST00000656751.1	n.85+608T>G		intron_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.37A>C (p.I13L) alteration is located in exon 1 (coding exon 1) of the IER3 gene. This alteration results from a A to C substitution at nucleotide position 37, causing the isoleucine (I) at amino acid position 13 to be replaced by a leucine (L). 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	Benign	0.091
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.014
Sift	Benign	0.19	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.0060	.;B
Vest4		0.094
MutPred		0.13		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.23
MPC		0.92
ClinPred		0.069	T
GERP RS		0.80
Varity_R		0.12
gMVP		0.17

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.

Other links and lift over

hg19: chr6-30712259;