Genetic Variant ING1:p.Ala192Val (chr13-110719667-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM2PM5BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.54

Publications

0 publications found

Variant links:

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

ING1 links:

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ACMG classification

Classification was made for transcript

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).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ING1	NM_198219.3	MANE Select	c.575C>T	p.Ala192Val	missense	Exon 2 of 2	NP_937862.1	Q9UK53-2
ING1	NM_005537.5		c.1004C>T	p.Ala335Val	missense	Exon 2 of 2	NP_005528.4	Q9UK53
ING1	NM_001267728.1		c.524C>T	p.Ala175Val	missense	Exon 2 of 2	NP_001254657.1	Q9UK53-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ING1	ENST00000333219.9	TSL:1 MANE Select	c.575C>T	p.Ala192Val	missense	Exon 2 of 2	ENSP00000328436.8	Q9UK53-2
ING1	ENST00000375774.3	TSL:1	c.1004C>T	p.Ala335Val	missense	Exon 2 of 2	ENSP00000364929.3	A0A0C4DFW2
ING1	ENST00000338450.7	TSL:1	c.443C>T	p.Ala148Val	missense	Exon 2 of 2	ENSP00000345202.7	Q9UK53-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.042

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.78

PhyloP100

3.5

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.1

REVEL

Benign

0.096

Sift

Uncertain

0.015

Sift4G

Benign

0.21

Polyphen

1.0

Vest4

0.22

MutPred

0.21

Gain of methylation at K334 (P = 0.0346)

MVP

0.70

MPC

1.8

ClinPred

0.93

GERP RS

5.3

gMVP

0.39

Mutation Taster

=28/72

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over