Genetic Variant ING3:p.Tyr149Tyr (chr7-120967539-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_019071.3(ING3):c.447T>C(p.Tyr149Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000441 in 1,547,670 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 3 hom. )

Consequence

ING3
NM_019071.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.899

Variant links:

Genes affected

ING3 (HGNC:14587): (inhibitor of growth family member 3) The protein encoded by this gene is similar to ING1, a tumor suppressor protein that can interact with TP53, inhibit cell growth, and induce apoptosis. This protein contains a PHD-finger, which is a common motif in proteins involved in chromatin remodeling. This gene can activate p53 trans-activated promoters, including promoters of p21/waf1 and bax. Overexpression of this gene has been shown to inhibit cell growth and induce apoptosis. Allelic loss and reduced expression of this gene were detected in head and neck cancers. Two alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2008]

ING3 links:

LOC124901734 (HGNC:):

LOC124901734 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-120967539-T-C is Benign according to our data. Variant chr7-120967539-T-C is described in ClinVar as [Benign]. Clinvar id is 778332.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.899 with no splicing effect.

BS2

High AC in GnomAd4 at 311 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ING3	NM_019071.3 link	c.447T>C	p.Tyr149Tyr	synonymous_variant	Exon 7 of 12	ENST00000315870.10	NP_061944.2	Q9NXR8-1
LOC124901734	XR_007060492.1 link	n.146-1706A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ING3	ENST00000315870.10 link	c.447T>C	p.Tyr149Tyr	synonymous_variant	Exon 7 of 12	1	NM_019071.3	ENSP00000320566.5		Q9NXR8-1

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

298

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000581

AC:

134

AN:

230582

Hom.:

AF XY:

0.000481

AC XY:

AN XY:

124862

show subpopulations

Gnomad AFR exome

AF:

0.00723

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000386

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000742

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.000267

AC:

372

AN:

1395354

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

162

AN XY:

695592

show subpopulations

Gnomad4 AFR exome

AF:

0.00806

Gnomad4 AMR exome

AF:

0.000494

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00204

AC:

311

AN:

152316

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

133

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00719

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.00229

Asia WGS

AF:

0.00434

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.4

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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