Genetic Variant ING5:p.Thr3Ile (chr2-241702073-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032329.6(ING5):c.8C>T(p.Thr3Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,390,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

ING5
NM_032329.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

Variant links:

Genes affected

ING5 (HGNC:19421): (inhibitor of growth family member 5) This gene encodes a tumor suppressor protein that inhibits cell growth and induces apoptosis. This protein contains a PHD-type zinc finger. It interacts with tumor suppressor p53 and p300, a component of the histone acetyl transferase complex, suggesting a role in transcriptional regulation. Alternative splicing and the use of multiple promoters and 3' terminal exons results in multiple transcript variants. [provided by RefSeq, Aug 2016]

ING5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38161454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ING5	NM_032329.6 link	c.8C>T	p.Thr3Ile	missense_variant	Exon 1 of 8	ENST00000313552.11	NP_115705.2	Q8WYH8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ING5	ENST00000313552.11 link	c.8C>T	p.Thr3Ile	missense_variant	Exon 1 of 8	1	NM_032329.6	ENSP00000322142.7		Q8WYH8-1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000161

AC:

AN:

1239490

Hom.:

Cov.:

AF XY:

0.00000164

AC XY:

AN XY:

611216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000200

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151212

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73854

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8C>T (p.T3I) alteration is located in exon 1 (coding exon 1) of the ING5 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the threonine (T) at amino acid position 3 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.25

B;.

Vest4

0.30

MutPred

0.26

Loss of disorder (P = 0.0614);Loss of disorder (P = 0.0614);

MVP

0.52

MPC

0.94

ClinPred

0.99

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over