12-6652731-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016162.4(ING4):c.428G>A(p.Arg143His) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
ING4
NM_016162.4 missense
NM_016162.4 missense
Scores
4
5
8
Clinical Significance
Conservation
PhyloP100: 5.75
Genes affected
ING4 (HGNC:19423): (inhibitor of growth family member 4) This gene encodes a tumor suppressor protein that contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling. This protein can bind TP53 and EP300/p300, a component of the histone acetyl transferase complex, suggesting its involvement in the TP53-dependent regulatory pathway. Multiple alternatively spliced transcript variants have been observed that encode distinct proteins. [provided by RefSeq, Jul 2008]
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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 | UniProt |
---|---|---|---|---|---|---|---|
ING4 | NM_016162.4 | c.428G>A | p.Arg143His | missense_variant | 5/8 | ENST00000341550.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ING4 | ENST00000341550.9 | c.428G>A | p.Arg143His | missense_variant | 5/8 | 1 | NM_016162.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152126Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251484Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135916
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GnomAD4 exome AF: 0.000113 AC: 165AN: 1461852Hom.: 0 Cov.: 31 AF XY: 0.0000976 AC XY: 71AN XY: 727234
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GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152126Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74304
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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 | Sep 07, 2022 | The c.431G>A (p.R144H) alteration is located in exon 5 (coding exon 5) of the ING4 gene. This alteration results from a G to A substitution at nucleotide position 431, causing the arginine (R) at amino acid position 144 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;D;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0, 1.0, 1.0
.;D;D;.;D;D
Vest4
MVP
MPC
1.9
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at