NM_016162.4:c.505G>A

Variant names:

• chr12-6652411-C-T
• NM_016162.4:c.505G>A

Variant summary

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

The NM_016162.4(ING4):​c.505G>A​(p.Glu169Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ING4 NM_016162.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.87
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.505G>A	p.Glu169Lys	missense	Exon 6 of 8	NP_057246.2
	ING4	NM_001127582.2		c.508G>A	p.Glu170Lys	missense	Exon 6 of 8	NP_001121054.1	Q9UNL4-1
	ING4	NM_001127583.2		c.499G>A	p.Glu167Lys	missense	Exon 6 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.505G>A	p.Glu169Lys	missense	Exon 6 of 8	ENSP00000343396.4	Q9UNL4-2
	ING4	ENST00000396807.8	TSL:1	c.508G>A	p.Glu170Lys	missense	Exon 6 of 8	ENSP00000380024.4	Q9UNL4-1
	ING4	ENST00000412586.6	TSL:1	c.499G>A	p.Glu167Lys	missense	Exon 6 of 8	ENSP00000412705.2	Q9UNL4-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727136

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.078
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.9
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.18
Sift	Benign	0.59	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.61
MutPred		0.41		Gain of MoRF binding (P = 0.0052)
MVP		0.65
MPC		0.78
ClinPred		0.74	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.50
Mutation Taster		=36/64	disease causing

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

hg19: chr12-6761577;