2-241711416-C-T

Variant names:

• chr2-241711416-C-T
• rs1238068993
• NM_032329.6:c.316C>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_032329.6(ING5):​c.316C>T​(p.Arg106Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000976 in 1,435,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: ING5 NM_032329.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.19

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ING5	NM_032329.6	c.316C>T	p.Arg106Cys	missense_variant	Exon 4 of 8	ENST00000313552.11	NP_115705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ING5	ENST00000313552.11	c.316C>T	p.Arg106Cys	missense_variant	Exon 4 of 8	1	NM_032329.6	ENSP00000322142.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000976 AC: 14 AN: 1435078 Hom.: 0 Cov.: 30 AF XY: 0.00000842 AC XY: 6 AN XY: 712978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000255

Gnomad4 ASJ exome AF: 0.0000393

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000242

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000909

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.316C>T (p.R106C) alteration is located in exon 4 (coding exon 4) of the ING5 gene. This alteration results from a C to T substitution at nucleotide position 316, causing the arginine (R) at amino acid position 106 to be replaced by a cysteine (C). 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	0.87
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.61	.;D;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.2	.;M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.7	.;D;D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	.;D;D
Sift4G	Pathogenic	0.0010	.;D;D
Polyphen		1.0	.;D;.
Vest4		0.83, 0.81
MutPred		0.46		.;Loss of MoRF binding (P = 0.014);Loss of MoRF binding (P = 0.014);
MVP		0.59
MPC		2.1
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.84
gMVP		0.75

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

Other links and lift over

dbSNP: rs1238068993; hg19: chr2-242650831;