chr2-241711416-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032329.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING5	NM_032329.6	MANE Select	c.316C>T	p.Arg106Cys	missense	Exon 4 of 8	NP_115705.2
	ING5	NM_001330161.2		c.322C>T	p.Arg108Cys	missense	Exon 5 of 8	NP_001317090.1	A0A1B0GW41
	ING5	NM_001330162.2		c.316C>T	p.Arg106Cys	missense	Exon 4 of 8	NP_001317091.1	Q8WYH8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING5	ENST00000313552.11	TSL:1 MANE Select	c.316C>T	p.Arg106Cys	missense	Exon 4 of 8	ENSP00000322142.7	Q8WYH8-1
	ING5	ENST00000406941.5	TSL:1	c.316C>T	p.Arg106Cys	missense	Exon 4 of 8	ENSP00000385937.1	Q8WYH8-2
	ING5	ENST00000948226.1		c.316C>T	p.Arg106Cys	missense	Exon 4 of 10	ENSP00000618285.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000867 AC: 2 AN: 230720 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31570

American (AMR) AF: 0.0000255 AC: 1 AN: 39270

Ashkenazi Jewish (ASJ) AF: 0.0000393 AC: 1 AN: 25422

East Asian (EAS) AF: 0.00 AC: 0 AN: 38042

South Asian (SAS) AF: 0.0000242 AC: 2 AN: 82496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000909 AC: 10 AN: 1100336

Other (OTH) AF: 0.00 AC: 0 AN: 59132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000141743), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.2
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.7	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.46		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
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs1238068993; hg19: chr2-242650831;