Variant 5-5441118-T-A 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.204T>A(p.Asn68Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 152,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ICE1
NM_015325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.02

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:

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=0.08091968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICE1	NM_015325.3 linkuse as main transcript	c.204T>A	p.Asn68Lys	missense_variant	5/19	ENST00000296564.9	NP_056140.1	Q9Y2F5
ICE1	XM_011513999.3 linkuse as main transcript	c.204T>A	p.Asn68Lys	missense_variant	5/17		XP_011512301.1
ICE1	XM_047417046.1 linkuse as main transcript	c.204T>A	p.Asn68Lys	missense_variant	5/14		XP_047273002.1
ICE1	XM_047417047.1 linkuse as main transcript	c.204T>A	p.Asn68Lys	missense_variant	5/15		XP_047273003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICE1	ENST00000296564.9 linkuse as main transcript	c.204T>A	p.Asn68Lys	missense_variant	5/19	1	NM_015325.3	ENSP00000296564.7		Q9Y2F5
ICE1	ENST00000512608 linkuse as main transcript	c.-28T>A		5_prime_UTR_variant	5/11	4		ENSP00000485617.1		A0A096LPH9

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000603

AC:

AN:

165906

Hom.:

AF XY:

0.00

AC XY:

AN XY:

87488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000395

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1379556

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682778

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ExAC

AF:

0.00000873

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

Oct 28, 2024

The c.204T>A (p.N68K) alteration is located in exon 5 (coding exon 5) of the ICE1 gene. This alteration results from a T to A substitution at nucleotide position 204, causing the asparagine (N) at amino acid position 68 to be replaced by a lysine (K). 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

Pathogenic

0.95

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.056

Eigen

Benign

-0.80

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.72

M_CAP

Benign

0.023

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.97

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.21

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.71

MutPred

0.13

Gain of ubiquitination at N68 (P = 0.0075);

MVP

0.12

MPC

0.51

ClinPred

0.63

GERP RS

-8.1

Varity_R

0.30

gMVP

0.32

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

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