Genetic Variant NM_203434.3:c.727C>T (chr9-129177326-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203434.3(IER5L):c.727C>T(p.Pro243Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,379,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P243L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

IER5L
NM_203434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Publications

0 publications found

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 was made for transcript

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=0.17463464).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203434.3. 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
	IER5L	NM_203434.3	MANE Select	c.727C>T	p.Pro243Ser	missense	Exon 1 of 1	NP_982258.2	Q5T953-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IER5L	ENST00000372491.4	TSL:6 MANE Select	c.727C>T	p.Pro243Ser	missense	Exon 1 of 1	ENSP00000361569.2	Q5T953-1
ENSG00000235007	ENST00000674648.1		c.109-31543G>A		intron	N/A	ENSP00000502744.1	A0A6Q8PH23
IER5L-AS1	ENST00000372490.4	TSL:2	n.367+189G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151972

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000252

AC:

AN:

119276

AF XY:

0.0000441

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000484

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000187

AC:

AN:

1227642

Hom.:

Cov.:

AF XY:

0.0000216

AC XY:

AN XY:

601256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25950

American (AMR)

AF:

0.00

AC:

AN:

21668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18478

East Asian (EAS)

AF:

0.00

AC:

AN:

31282

South Asian (SAS)

AF:

0.00

AC:

AN:

48834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4054

European-Non Finnish (NFE)

AF:

0.0000201

AC:

AN:

997456

Other (OTH)

AF:

0.0000603

AC:

AN:

49730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41404

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67952

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000254

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0019

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.58

M_CAP

Benign

0.049

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

PhyloP100

1.2

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.2

REVEL

Benign

0.12

Sift

Benign

0.31

Sift4G

Benign

0.34

Polyphen

0.0090

Vest4

0.23

MutPred

0.76

Gain of glycosylation at P243 (P = 0.0828)

MVP

0.043

MPC

0.91

ClinPred

0.061

GERP RS

1.9

Varity_R

0.066

gMVP

0.20

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over