13-110719667-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_198219.3(ING1):​c.575C>T​(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. In-silico tool predicts a benign outcome for this variant. 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: 32)
• 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.

• PM2: Very rare variant in population databases, with high coverage
• 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.25056472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ING1	NM_198219.3	c.575C>T	p.Ala192Val	missense_variant	Exon 2 of 2	ENST00000333219.9	NP_937862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ING1	ENST00000333219.9	c.575C>T	p.Ala192Val	missense_variant	Exon 2 of 2	1	NM_198219.3	ENSP00000328436.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	.;.;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.78	T
PhyloP100		3.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.096
Sift	Uncertain	0.015	D;D;D;T
Sift4G	Benign	0.21	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.22
MutPred		0.21		.;.;.;Gain of methylation at K334 (P = 0.0346);
MVP		0.70
MPC		1.8
ClinPred		0.93	D
GERP RS		5.3
gMVP		0.39
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs121909252; hg19: chr13-111372014; COSMIC: COSV58166814; COSMIC: COSV58166814;