chr2-241702078-A-T

Variant names:

• chr2-241702078-A-T
• rs979210386
• NM_032329.6:c.13A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_032329.6(ING5):​c.13A>T​(p.Met5Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000036 in 1,387,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ING5 NM_032329.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.33
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09199235).
• BS2: High AC in GnomAd4 at 33 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.13A>T	p.Met5Leu	missense	Exon 1 of 8	NP_115705.2
	ING5	NM_001330162.2		c.13A>T	p.Met5Leu	missense	Exon 1 of 8	NP_001317091.1	Q8WYH8-2
	ING5	NM_001330161.2		c.44-2575A>T		intron	N/A	NP_001317090.1	A0A1B0GW41

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING5	ENST00000313552.11	TSL:1 MANE Select	c.13A>T	p.Met5Leu	missense	Exon 1 of 8	ENSP00000322142.7	Q8WYH8-1
	ING5	ENST00000406941.5	TSL:1	c.13A>T	p.Met5Leu	missense	Exon 1 of 8	ENSP00000385937.1	Q8WYH8-2
	ING5	ENST00000948226.1		c.13A>T	p.Met5Leu	missense	Exon 1 of 10	ENSP00000618285.1

Frequencies

GnomAD3 genomes AF: 0.000214 AC: 32 AN: 149672 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000712

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000149 AC: 1 AN: 66908 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000975

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: 0.0000137 AC: 17 AN: 1238218 Hom.: 0 Cov.: 30 AF XY: 0.0000164 AC XY: 10 AN XY: 610624

African (AFR) AF: 0.000491 AC: 12 AN: 24430

American (AMR) AF: 0.0000515 AC: 1 AN: 19410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20182

East Asian (EAS) AF: 0.00 AC: 0 AN: 25052

South Asian (SAS) AF: 0.00 AC: 0 AN: 63998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5008

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 998198

Other (OTH) AF: 0.0000809 AC: 4 AN: 49422

GnomAD4 genome AF: 0.000220 AC: 33 AN: 149778 Hom.: 0 Cov.: 33 AF XY: 0.000246 AC XY: 18 AN XY: 73196

African (AFR) AF: 0.000734 AC: 30 AN: 40876

American (AMR) AF: 0.000199 AC: 3 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5004

South Asian (SAS) AF: 0.00 AC: 0 AN: 4762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9982

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67332

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000238

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	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.92	D
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.17	N
PhyloP100		4.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.056
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.35		Loss of disorder (P = 0.159)
MVP		0.29
MPC		0.69
ClinPred		0.19	T
GERP RS		3.2
PromoterAI		-0.31	Neutral
Varity_R		0.43
Mutation Taster		=76/24	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: rs979210386; hg19: chr2-242641493; COSMIC: COSV107374714;