chr9-129177305-A-C

Variant names:

• chr9-129177305-A-C
• rs765030656
• NM_203434.3:c.748T>G

Variant summary

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

The NM_203434.3(IER5L):​c.748T>G​(p.Cys250Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000318 in 1,259,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: IER5L NM_203434.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.748T>G	p.Cys250Gly	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.748T>G	p.Cys250Gly	missense	Exon 1 of 1	ENSP00000361569.2	Q5T953-1
	ENSG00000235007	ENST00000674648.1		c.109-31564A>C		intron	N/A	ENSP00000502744.1	A0A6Q8PH23
	IER5L-AS1	ENST00000372490.4	TSL:2	n.367+168A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000237 AC: 3 AN: 126532 AF XY: 0.0000139

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000318 AC: 4 AN: 1259840 Hom.: 0 Cov.: 31 AF XY: 0.00000322 AC XY: 2 AN XY: 620980

African (AFR) AF: 0.00 AC: 0 AN: 25496

American (AMR) AF: 0.000176 AC: 4 AN: 22728

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18870

East Asian (EAS) AF: 0.00 AC: 0 AN: 30720

South Asian (SAS) AF: 0.00 AC: 0 AN: 59896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1015222

Other (OTH) AF: 0.00 AC: 0 AN: 50956

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000253 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.32
Sift	Benign	0.088	T
Sift4G	Benign	0.57	T
Polyphen		0.99	D
Vest4		0.48
MutPred		0.79		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.043
MPC		1.1
ClinPred		0.59	D
GERP RS		2.9
Varity_R		0.24
gMVP		0.31
Mutation Taster		=82/18	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: rs765030656; hg19: chr9-131939584;