12-6663087-C-A

Position:

• chr12-6663087-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016162.4(ING4):​c.15G>T​(p.Met5Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ING4 NM_016162.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

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]

ING4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32797194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ING4	NM_016162.4	c.15G>T	p.Met5Ile	missense_variant	1/8	ENST00000341550.9	NP_057246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ING4	ENST00000341550.9	c.15G>T	p.Met5Ile	missense_variant	1/8	1	NM_016162.4	ENSP00000343396.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

The c.15G>T (p.M5I) alteration is located in exon 1 (coding exon 1) of the ING4 gene. This alteration results from a G to T substitution at nucleotide position 15, causing the methionine (M) at amino acid position 5 to be replaced by an isoleucine (I). 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	0.81
BayesDel_addAF	Benign	0.0024	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	.;T;T;.;.;.;.
Eigen	Benign	-0.097
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.33	T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N;.;N;N;N;N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.56	N;.;N;N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.59	T;.;T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T;T;T
Polyphen		0.0010, 0.013, 0.0020, 0.028	.;.;B;B;.;B;B
Vest4		0.81
MutPred		0.43		Gain of catalytic residue at M5 (P = 0);Gain of catalytic residue at M5 (P = 0);Gain of catalytic residue at M5 (P = 0);Gain of catalytic residue at M5 (P = 0);Gain of catalytic residue at M5 (P = 0);Gain of catalytic residue at M5 (P = 0);Gain of catalytic residue at M5 (P = 0);
MVP		0.64
MPC		0.78
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.57
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-6772253;