Variant 9-129177151-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_203434.3(IER5L):c.902A>C(p.Lys301Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IER5L
NM_203434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

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

IER5L links:

ENSG00000235007 (HGNC:):

ENSG00000235007 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.28146815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER5L	NM_203434.3 linkuse as main transcript	c.902A>C	p.Lys301Thr	missense_variant	1/1	ENST00000372491.4	NP_982258.2	Q5T953-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER5L	ENST00000372491.4 linkuse as main transcript	c.902A>C	p.Lys301Thr	missense_variant	1/1	6	NM_203434.3	ENSP00000361569.2		Q5T953-1
ENSG00000235007	ENST00000674648.1 linkuse as main transcript	c.109-31718T>G		intron_variant				ENSP00000502744.1		A0A6Q8PH23

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150620

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000974

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000254

AC:

323

AN:

1269970

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

142

AN XY:

620496

show subpopulations

Gnomad4 AFR exome

AF:

0.000404

Gnomad4 AMR exome

AF:

0.000139

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.000221

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.000564

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.000386

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000398

AC:

AN:

150748

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73592

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000200

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000974

Gnomad4 NFE

AF:

0.0000445

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.902A>C (p.K301T) alteration is located in exon 1 (coding exon 1) of the IER5L gene. This alteration results from a A to C substitution at nucleotide position 902, causing the lysine (K) at amino acid position 301 to be replaced by a threonine (T). 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

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.59

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.8

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.041

Polyphen

1.0

Vest4

0.27

MutPred

0.50

Loss of methylation at K301 (P = 1e-04);

MVP

0.043

MPC

1.1

ClinPred

0.69

GERP RS

3.2

Varity_R

0.24

gMVP

0.40

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