Variant 5-5457359-C-T 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.719C>T(p.Ser240Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ICE1
NM_015325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.230

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:

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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=0.07116839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ICE1	NM_015325.3 link	c.719C>T	p.Ser240Phe	missense_variant	12/19	ENST00000296564.9	NP_056140.1	Q9Y2F5
ICE1	XM_011513999.3 link	c.719C>T	p.Ser240Phe	missense_variant	12/17		XP_011512301.1
ICE1	XM_047417046.1 link	c.719C>T	p.Ser240Phe	missense_variant	12/14		XP_047273002.1
ICE1	XM_047417047.1 link	c.719C>T	p.Ser240Phe	missense_variant	12/15		XP_047273003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ICE1	ENST00000296564.9 link	c.719C>T	p.Ser240Phe	missense_variant	12/19	1	NM_015325.3	ENSP00000296564.7		Q9Y2F5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247548

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000584

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

AF:

0.00000137

AC:

AN:

1459746

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

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

Cov.:

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 24, 2024

The c.719C>T (p.S240F) alteration is located in exon 12 (coding exon 12) of the ICE1 gene. This alteration results from a C to T substitution at nucleotide position 719, causing the serine (S) at amino acid position 240 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.58

M_CAP

Benign

0.017

MetaRNN

Benign

0.071

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.018

Sift

Uncertain

0.019

Sift4G

Benign

0.12

Polyphen

0.0090

Vest4

0.25

MutPred

0.31

Loss of glycosylation at S240 (P = 0.0035);

MVP

0.043

MPC

0.31

ClinPred

0.37

GERP RS

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.063

gMVP

0.18

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