rs121909252

chr13-110719667-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_198219.3(ING1):c.575C>A(p.Ala192Asp) 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ING1 NM_198219.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.54

Genes affected

ING1 (HGNC:6062): (inhibitor of growth family member 1) This gene encodes a tumor suppressor protein that can induce cell growth arrest and apoptosis. The encoded protein is a nuclear protein that physically interacts with the tumor suppressor protein TP53 and is a component of the p53 signaling pathway. Reduced expression and rearrangement of this gene have been detected in various cancers. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. [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
• PP5: Variant 13-110719667-C-A is Pathogenic according to our data. Variant chr13-110719667-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 8069.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.26432085).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ING1	NM_198219.3	c.575C>A	p.Ala192Asp	missense_variant	2/2	ENST00000333219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ING1	ENST00000333219.9	c.575C>A	p.Ala192Asp	missense_variant	2/2	1	NM_198219.3	P1
ING1	ENST00000375774.3	c.1004C>A	p.Ala335Asp	missense_variant	2/2	1
ING1	ENST00000338450.7	c.443C>A	p.Ala148Asp	missense_variant	2/2	1
ING1	ENST00000375775.4	c.368C>A	p.Ala123Asp	missense_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Squamous cell carcinoma of the head and neck Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 15, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
Cadd	Pathogenic	27
Dann	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.013	D;T;T;D
Sift4G	Benign	0.32	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.29
MutPred		0.27		.;.;.;Gain of relative solvent accessibility (P = 0.0249);
MVP		0.72
MPC		2.5
ClinPred		0.97	D
GERP RS		5.3
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

LitVar

Other links and lift over

dbSNP: rs121909252; hg19: chr13-111372014;