rs193921122

Variant names:

• chr12-6653001-G-T
• rs193921122
• NM_016162.4:c.326C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-6653001-G-T
• chr12-6653001-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016162.4(ING4):​c.326C>A​(p.Ala109Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ING4 NM_016162.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.63
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

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.326C>A	p.Ala109Asp	missense	Exon 4 of 8	NP_057246.2
	ING4	NM_001127582.2		c.326C>A	p.Ala109Asp	missense	Exon 4 of 8	NP_001121054.1	Q9UNL4-1
	ING4	NM_001127583.2		c.326C>A	p.Ala109Asp	missense	Exon 4 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.326C>A	p.Ala109Asp	missense	Exon 4 of 8	ENSP00000343396.4	Q9UNL4-2
	ING4	ENST00000396807.8	TSL:1	c.326C>A	p.Ala109Asp	missense	Exon 4 of 8	ENSP00000380024.4	Q9UNL4-1
	ING4	ENST00000412586.6	TSL:1	c.326C>A	p.Ala109Asp	missense	Exon 4 of 8	ENSP00000412705.2	Q9UNL4-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.24
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.056	T
Polyphen		0.92	P
Vest4		0.77
MutPred		0.34		Loss of helix (P = 0.0558)
MVP		0.87
MPC		1.8
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.57
gMVP		0.61
Mutation Taster		=36/64	disease causing

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

Other links and lift over

dbSNP: rs193921122; hg19: chr12-6762167; COSMIC: COSV58556634; COSMIC: COSV58556634;