Variant 5-5436470-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015325.3(ICE1):c.137A>G(p.Asn46Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000184 in 1,471,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ICE1
NM_015325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

Variant links:

Genes affected

ICE1 (HGNC:29154): (interactor of little elongation complex ELL subunit 1) Enables protein-macromolecule adaptor activity. Involved in several processes, including positive regulation of intracellular protein transport; positive regulation of transcription by RNA polymerase III; and snRNA transcription. Located in Cajal body; histone locus body; and transcriptionally active chromatin. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ICE1 links:

ICE1 (HGNC:):

ICE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.23670852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICE1	NM_015325.3 linkuse as main transcript	c.137A>G	p.Asn46Ser	missense_variant	2/19	ENST00000296564.9	NP_056140.1	Q9Y2F5
ICE1	XM_011513999.3 linkuse as main transcript	c.137A>G	p.Asn46Ser	missense_variant	2/17		XP_011512301.1
ICE1	XM_047417046.1 linkuse as main transcript	c.137A>G	p.Asn46Ser	missense_variant	2/14		XP_047273002.1
ICE1	XM_047417047.1 linkuse as main transcript	c.137A>G	p.Asn46Ser	missense_variant	2/15		XP_047273003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ICE1	ENST00000296564.9 linkuse as main transcript	c.137A>G	p.Asn46Ser	missense_variant	2/19	1	NM_015325.3	ENSP00000296564.7	Q9Y2F5
ICE1	ENST00000512608 linkuse as main transcript	c.-95A>G		5_prime_UTR_variant	2/11	4		ENSP00000485617.1	A0A096LPH9
ICE1	ENST00000505464.1 linkuse as main transcript	n.311A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000257

AC:

AN:

155844

Hom.:

AF XY:

0.0000352

AC XY:

AN XY:

85200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000645

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000588

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000197

AC:

AN:

1318838

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

654762

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000389

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000150

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000223

Gnomad4 OTH exome

AF:

0.0000184

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000246

AC:

ExAC

AF:

0.0000333

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2024

The c.137A>G (p.N46S) alteration is located in exon 2 (coding exon 2) of the ICE1 gene. This alteration results from a A to G substitution at nucleotide position 137, causing the asparagine (N) at amino acid position 46 to be replaced by a serine (S). 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

0.25

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0088

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.7

REVEL

Benign

0.091

Sift

Uncertain

0.016

Sift4G

Uncertain

0.030

Polyphen

0.99

Vest4

0.45

MVP

0.068

MPC

0.40

ClinPred

0.59

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over