7-120953357-A-C

Variant names:

• chr7-120953357-A-C
• NM_019071.3:c.154A>C

Variant summary

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

The NM_019071.3(ING3):​c.154A>C​(p.Lys52Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ING3 NM_019071.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.14

Genes affected

ING3 (HGNC:14587): (inhibitor of growth family member 3) The protein encoded by this gene is similar to ING1, a tumor suppressor protein that can interact with TP53, inhibit cell growth, and induce apoptosis. This protein contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling. This gene can activate p53 trans-activated promoters, including promoters of p21/waf1 and bax. Overexpression of this gene has been shown to inhibit cell growth and induce apoptosis. Allelic loss and reduced expression of this gene were detected in head and neck cancers. Two alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
ING3	NM_019071.3	c.154A>C	p.Lys52Gln	missense_variant	Exon 3 of 12	ENST00000315870.10	NP_061944.2
ING3	NM_198267.2	c.154A>C	p.Lys52Gln	missense_variant	Exon 3 of 5		NP_938008.1
ING3	XM_047420535.1	c.154A>C	p.Lys52Gln	missense_variant	Exon 3 of 5		XP_047276491.1
ING3	XM_017012369.3	c.154A>C	p.Lys52Gln	missense_variant	Exon 3 of 5		XP_016867858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ING3	ENST00000315870.10	c.154A>C	p.Lys52Gln	missense_variant	Exon 3 of 12	1	NM_019071.3	ENSP00000320566.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.154A>C (p.K52Q) alteration is located in exon 3 (coding exon 3) of the ING3 gene. This alteration results from a A to C substitution at nucleotide position 154, causing the lysine (K) at amino acid position 52 to be replaced by a glutamine (Q). 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	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.;T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.53	D;D;D;D
MetaSVM	Pathogenic	0.90	D
MutationAssessor	Uncertain	2.4	M;M;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Uncertain	0.58
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.014	D;T;D;D
Polyphen		0.99	D;D;.;.
Vest4		0.58
MutPred		0.27		Loss of ubiquitination at K52 (P = 0.0183);Loss of ubiquitination at K52 (P = 0.0183);Loss of ubiquitination at K52 (P = 0.0183);.;
MVP		0.91
MPC		1.6
ClinPred		0.92	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-120593411;