13-110719667-CC-TT

Variant names:

• chr13-110719667-CC-TT
• NM_198219.3:c.575_576delCCinsTT
• ING1 p.Ala192Val

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_198219.3(ING1):​c.575_576delCCinsTT​(p.Ala192Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A192D) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ING1 NM_198219.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54
• Publications: 0 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.

• PM5: Other missense variant is known to change same aminoacid residue: 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.

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.575_576delCCinsTT	p.Ala192Val	missense	N/A	NP_937862.1	Q9UK53-2
	ING1	NM_005537.5		c.1004_1005delCCinsTT	p.Ala335Val	missense	N/A	NP_005528.4	Q9UK53
	ING1	NM_001267728.1		c.524_525delCCinsTT	p.Ala175Val	missense	N/A	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.575_576delCCinsTT	p.Ala192Val	missense	N/A	ENSP00000328436.8	Q9UK53-2
	ING1	ENST00000375774.3	TSL:1	c.1004_1005delCCinsTT	p.Ala335Val	missense	N/A	ENSP00000364929.3	A0A0C4DFW2
	ING1	ENST00000338450.7	TSL:1	c.443_444delCCinsTT	p.Ala148Val	missense	N/A	ENSP00000345202.7	Q9UK53-4

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-111372014;