5-5444315-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015325.3(ICE1):ā€‹c.413A>Gā€‹(p.Lys138Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,414,862 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

ICE1
NM_015325.3 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ICE1NM_015325.3 linkc.413A>G p.Lys138Arg missense_variant 7/19 ENST00000296564.9 NP_056140.1 Q9Y2F5
ICE1XM_011513999.3 linkc.413A>G p.Lys138Arg missense_variant 7/17 XP_011512301.1
ICE1XM_047417046.1 linkc.413A>G p.Lys138Arg missense_variant 7/14 XP_047273002.1
ICE1XM_047417047.1 linkc.413A>G p.Lys138Arg missense_variant 7/15 XP_047273003.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ICE1ENST00000296564.9 linkc.413A>G p.Lys138Arg missense_variant 7/191 NM_015325.3 ENSP00000296564.7 Q9Y2F5
ICE1ENST00000512608.5 linkc.182A>G p.Lys61Arg missense_variant 7/114 ENSP00000485617.1 A0A096LPH9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000550
AC:
1
AN:
181678
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
96224
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000134
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.07e-7
AC:
1
AN:
1414862
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
699210
show subpopulations
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:
9.21e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0
ExAC
AF:
0.00000845
AC:
1

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 submitterclinical testingAmbry GeneticsSep 14, 2023The c.413A>G (p.K138R) alteration is located in exon 7 (coding exon 7) of the ICE1 gene. This alteration results from a A to G substitution at nucleotide position 413, causing the lysine (K) at amino acid position 138 to be replaced by an arginine (R). 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
0.15
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
.;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.7
.;N
REVEL
Benign
0.15
Sift
Benign
0.10
.;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.39
MutPred
0.28
.;Gain of methylation at K136 (P = 0.2263);
MVP
0.24
MPC
0.43
ClinPred
0.73
D
GERP RS
5.5
Varity_R
0.12
gMVP
0.073

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.36
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.36
Position offset: -5

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.

Other links and lift over

dbSNP: rs772241143; hg19: chr5-5444428; API