rs193921122

Positions:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016162.4(ING4):​c.326C>T​(p.Ala109Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ING4 NM_016162.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ING4	NM_016162.4	c.326C>T	p.Ala109Val	missense_variant	4/8	ENST00000341550.9	NP_057246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ING4	ENST00000341550.9	c.326C>T	p.Ala109Val	missense_variant	4/8	1	NM_016162.4	ENSP00000343396.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	.;T;.;.;.;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.7	D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D;T;D;T;D
Sift4G	Benign	0.072	T;T;T;D;T;T
Polyphen		0.98, 1.0, 0.99, 1.0	.;D;D;.;D;D
Vest4		0.66
MutPred		0.27		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;
MVP		0.87
MPC		1.5
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.50
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs193921122; hg19: chr12-6762167; COSMIC: COSV58556744; COSMIC: COSV58556744;