chr9-129177113-C-T

Variant names:

• chr9-129177113-C-T
• rs766687104
• NM_203434.3:c.940G>A

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.940G>A​(p.Asp314Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,307,638 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. 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. D314H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: IER5L NM_203434.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• 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=0.11941892).

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.940G>A	p.Asp314Asn	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.940G>A	p.Asp314Asn	missense	Exon 1 of 1	ENSP00000361569.2	Q5T953-1
	ENSG00000235007	ENST00000674648.1		c.109-31756C>T		intron	N/A	ENSP00000502744.1	A0A6Q8PH23
	IER5L-AS1	ENST00000372490.4	TSL:2	n.343C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1307638 Hom.: 0 Cov.: 33 AF XY: 0.00000157 AC XY: 1 AN XY: 638302

African (AFR) AF: 0.00 AC: 0 AN: 25902

American (AMR) AF: 0.00 AC: 0 AN: 20252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18796

East Asian (EAS) AF: 0.00 AC: 0 AN: 32436

South Asian (SAS) AF: 0.00 AC: 0 AN: 65732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5192

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1039908

Other (OTH) AF: 0.00 AC: 0 AN: 53884

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.0
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.098
Sift	Benign	0.17	T
Sift4G	Benign	0.44	T
Polyphen		0.0020	B
Vest4		0.10
MutPred		0.37		Loss of loop (P = 0.0986)
MVP		0.12
MPC		0.88
ClinPred		0.24	T
GERP RS		2.3
Varity_R		0.12
gMVP		0.10
Mutation Taster		=93/7	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: rs766687104; hg19: chr9-131939392;