12-6652690-C-T

Variant names:

• chr12-6652690-C-T
• rs764644678
• NM_016162.4:c.469G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016162.4(ING4):​c.469G>A​(p.Ala157Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A157P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ING4 NM_016162.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15041152).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016162.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING4	NM_016162.4	MANE Select	c.469G>A	p.Ala157Thr	missense	Exon 5 of 8	NP_057246.2
	ING4	NM_001127582.2		c.472G>A	p.Ala158Thr	missense	Exon 5 of 8	NP_001121054.1	Q9UNL4-1
	ING4	NM_001127583.2		c.463G>A	p.Ala155Thr	missense	Exon 5 of 8	NP_001121055.1	Q9UNL4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING4	ENST00000341550.9	TSL:1 MANE Select	c.469G>A	p.Ala157Thr	missense	Exon 5 of 8	ENSP00000343396.4	Q9UNL4-2
	ING4	ENST00000396807.8	TSL:1	c.472G>A	p.Ala158Thr	missense	Exon 5 of 8	ENSP00000380024.4	Q9UNL4-1
	ING4	ENST00000412586.6	TSL:1	c.463G>A	p.Ala155Thr	missense	Exon 5 of 8	ENSP00000412705.2	Q9UNL4-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.057
Sift	Benign	0.29	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.33		Gain of phosphorylation at A158 (P = 0.0055)
MVP		0.68
MPC		0.67
ClinPred		0.48	T
GERP RS		2.8
Varity_R		0.035
gMVP		0.46
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs764644678; hg19: chr12-6761856; COSMIC: COSV58556122; COSMIC: COSV58556122;