9-129176914-G-T

Position:

• chr9-129176914-G-T

Variant summary

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

The NM_203434.3(IER5L):​c.1139C>A​(p.Pro380Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,451,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: IER5L NM_203434.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.904

Genes affected

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

ENSG00000235007 (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=0.2280479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER5L	NM_203434.3	c.1139C>A	p.Pro380Gln	missense_variant	1/1	ENST00000372491.4	NP_982258.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER5L	ENST00000372491.4	c.1139C>A	p.Pro380Gln	missense_variant	1/1	6	NM_203434.3	ENSP00000361569.2
ENSG00000235007	ENST00000674648.1	c.109-31955G>T		intron_variant				ENSP00000502744.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000454 AC: 1 AN: 220084 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122288

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000105

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000551 AC: 8 AN: 1451940 Hom.: 0 Cov.: 33 AF XY: 0.00000554 AC XY: 4 AN XY: 722068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

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: 0.00000541

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

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

Nov 15, 2021

The c.1139C>A (p.P380Q) alteration is located in exon 1 (coding exon 1) of the IER5L gene. This alteration results from a C to A substitution at nucleotide position 1139, causing the proline (P) at amino acid position 380 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0028	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.11
Sift	Uncertain	0.013	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.46		Loss of glycosylation at P380 (P = 0.0058);
MVP		0.043
MPC		0.84
ClinPred		0.38	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.13

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

Other links and lift over

dbSNP: rs1181292315; hg19: chr9-131939193;