rs121909251

Variant names:

• chr13-110719739-A-G
• rs121909251
• NM_198219.3:c.647A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_198219.3(ING1):​c.647A>G​(p.Asn216Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ING1 NM_198219.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.94
• Publications: 4 publications found

Genes affected

ING1 (HGNC:6062): (inhibitor of growth family member 1) This gene encodes a tumor suppressor protein that can induce cell growth arrest and apoptosis. The encoded protein is a nuclear protein that physically interacts with the tumor suppressor protein TP53 and is a component of the p53 signaling pathway. Reduced expression and rearrangement of this gene have been detected in various cancers. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ING1 Gene-Disease associations (from GenCC):

• head and neck squamous cell carcinoma

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-110719739-A-G is Pathogenic according to our data. Variant chr13-110719739-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 8068.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING1	NM_198219.3	MANE Select	c.647A>G	p.Asn216Ser	missense	Exon 2 of 2	NP_937862.1
	ING1	NM_005537.5		c.1076A>G	p.Asn359Ser	missense	Exon 2 of 2	NP_005528.4
	ING1	NM_001267728.1		c.596A>G	p.Asn199Ser	missense	Exon 2 of 2	NP_001254657.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ING1	ENST00000333219.9	TSL:1 MANE Select	c.647A>G	p.Asn216Ser	missense	Exon 2 of 2	ENSP00000328436.8
	ING1	ENST00000375774.3	TSL:1	c.1076A>G	p.Asn359Ser	missense	Exon 2 of 2	ENSP00000364929.3
	ING1	ENST00000338450.7	TSL:1	c.515A>G	p.Asn172Ser	missense	Exon 2 of 2	ENSP00000345202.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Squamous cell carcinoma of the head and neck (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.53	T
PhyloP100		6.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.013	D
Sift4G	Benign	0.14	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.55		Gain of catalytic residue at S362 (P = 0)
MVP		0.81
MPC		1.8
ClinPred		0.98	D
GERP RS		5.4
gMVP		0.52
Mutation Taster		=30/70	disease causing (ClinVar)

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: rs121909251; hg19: chr13-111372086;