NM_203434.3:c.988C>T

Variant names:

• chr9-129177065-G-A
• NM_203434.3:c.988C>T

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.988C>T​(p.Pro330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,351,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: IER5L NM_203434.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.753
• 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=0.1918501).

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.988C>T	p.Pro330Ser	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.988C>T	p.Pro330Ser	missense	Exon 1 of 1	ENSP00000361569.2	Q5T953-1
	ENSG00000235007	ENST00000674648.1		c.109-31804G>A		intron	N/A	ENSP00000502744.1	A0A6Q8PH23
	IER5L-AS1	ENST00000372490.4	TSL:2	n.295G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1351520 Hom.: 0 Cov.: 33 AF XY: 0.00000151 AC XY: 1 AN XY: 663984

African (AFR) AF: 0.00 AC: 0 AN: 27504

American (AMR) AF: 0.00 AC: 0 AN: 28460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21904

East Asian (EAS) AF: 0.00 AC: 0 AN: 32838

South Asian (SAS) AF: 0.00 AC: 0 AN: 73416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5336

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1059102

Other (OTH) AF: 0.00 AC: 0 AN: 55582

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Benign	0.092
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.75
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.096
Sift	Benign	0.085	T
Sift4G	Uncertain	0.025	D
Polyphen		0.90	P
Vest4		0.14
MutPred		0.59		Gain of phosphorylation at P330 (P = 0.0271)
MVP		0.043
MPC		0.91
ClinPred		0.21	T
GERP RS		2.3
Varity_R		0.074
gMVP		0.23
Mutation Taster		=80/20	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

hg19: chr9-131939344;