rs121909252

Variant names:

• chr13-110719667-C-A
• rs121909252
• NM_198219.3:c.575C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-110719667-C-A
• chr13-110719667-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 2 publications found

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]

ING1 Gene-Disease associations (from GenCC):

• head and neck squamous cell carcinoma

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198219.3. 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
	ING1	NM_198219.3	MANE Select	c.575C>A	p.Ala192Asp	missense	Exon 2 of 2	NP_937862.1	Q9UK53-2
	ING1	NM_005537.5		c.1004C>A	p.Ala335Asp	missense	Exon 2 of 2	NP_005528.4	Q9UK53
	ING1	NM_001267728.1		c.524C>A	p.Ala175Asp	missense	Exon 2 of 2	NP_001254657.1	Q9UK53-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING1	ENST00000333219.9	TSL:1 MANE Select	c.575C>A	p.Ala192Asp	missense	Exon 2 of 2	ENSP00000328436.8	Q9UK53-2
	ING1	ENST00000375774.3	TSL:1	c.1004C>A	p.Ala335Asp	missense	Exon 2 of 2	ENSP00000364929.3	A0A0C4DFW2
	ING1	ENST00000338450.7	TSL:1	c.443C>A	p.Ala148Asp	missense	Exon 2 of 2	ENSP00000345202.7	Q9UK53-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Squamous cell carcinoma of the head and neck (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.092	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.81	T
PhyloP100		3.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Benign	0.32	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
Mutation Taster		=2/98	disease causing (ClinVar)

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

dbSNP: rs121909252; hg19: chr13-111372014;