chr9-129177332-G-C

Variant names:

• chr9-129177332-G-C
• rs377514596
• NM_203434.3:c.721C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203434.3(IER5L):​c.721C>G​(p.Pro241Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000833 in 1,200,200 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P241S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: IER5L NM_203434.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 0 publications found

Genes affected

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

ENSG00000235007 (HGNC:):

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

ACMG classification

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=0.15492529).

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.721C>G	p.Pro241Ala	missense	Exon 1 of 1	NP_982258.2	Q5T953-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IER5L	ENST00000372491.4	TSL:6 MANE Select	c.721C>G	p.Pro241Ala	missense	Exon 1 of 1	ENSP00000361569.2	Q5T953-1
	ENSG00000235007	ENST00000674648.1		c.109-31537G>C		intron	N/A	ENSP00000502744.1	A0A6Q8PH23
	IER5L-AS1	ENST00000372490.4	TSL:2	n.367+195G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.33e-7 AC: 1 AN: 1200200 Hom.: 0 Cov.: 31 AF XY: 0.00000171 AC XY: 1 AN XY: 585042

African (AFR) AF: 0.00 AC: 0 AN: 25576

American (AMR) AF: 0.00 AC: 0 AN: 20078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17658

East Asian (EAS) AF: 0.00 AC: 0 AN: 31112

South Asian (SAS) AF: 0.00 AC: 0 AN: 42202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 982806

Other (OTH) AF: 0.0000206 AC: 1 AN: 48484

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.00088	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.089
Sift	Uncertain	0.013	D
Sift4G	Benign	0.99	T
Polyphen		0.062	B
Vest4		0.23
MutPred		0.75		Gain of sheet (P = 0.0266)
MVP		0.043
MPC		0.88
ClinPred		0.18	T
GERP RS		2.9
Varity_R		0.12
gMVP		0.18
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs377514596; hg19: chr9-131939611;