Genetic Variant IER5L:p.Ser232Ala (chr9-129177359-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203434.3(IER5L):c.694T>G(p.Ser232Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 931,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

IER5L
NM_203434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

IER5L (HGNC:23679): (immediate early response 5 like)

IER5L links:

ENSG00000235007 (HGNC:):

ENSG00000235007 links:

IER5L-AS1 (HGNC:55825): (IER5L antisense RNA 1)

IER5L-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14911932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IER5L	NM_203434.3 link	c.694T>G	p.Ser232Ala	missense_variant	Exon 1 of 1	ENST00000372491.4	NP_982258.2	Q5T953-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IER5L	ENST00000372491.4 link	c.694T>G	p.Ser232Ala	missense_variant	Exon 1 of 1	6	NM_203434.3	ENSP00000361569.2		Q5T953-1
ENSG00000235007	ENST00000674648.1 link	c.109-31510A>C		intron_variant	Intron 2 of 2			ENSP00000502744.1		A0A6Q8PH23

Frequencies

GnomAD3 genomes

AF:

0.0000141

AC:

AN:

141652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000309

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

789946

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

377268

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:

0.0000118

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000141

AC:

AN:

141652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68890

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000309

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.694T>G (p.S232A) alteration is located in exon 1 (coding exon 1) of the IER5L gene. This alteration results from a T to G substitution at nucleotide position 694, causing the serine (S) at amino acid position 232 to be replaced by an alanine (A). 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

0.094

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.00073

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.17

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.20

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.81

REVEL

Benign

0.050

Sift

Benign

0.46

Sift4G

Benign

0.82

Polyphen

0.13

Vest4

0.31

MutPred

0.43

Loss of glycosylation at S232 (P = 7e-04);

MVP

0.043

MPC

0.75

ClinPred

0.12

GERP RS

2.8

Varity_R

0.12

gMVP

0.12

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over