rs121909251

Positions:

• chr13-110719739-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 8068.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ING1	NM_198219.3	c.647A>G	p.Asn216Ser	missense_variant	2/2	ENST00000333219.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ING1	ENST00000333219.9	c.647A>G	p.Asn216Ser	missense_variant	2/2	1	NM_198219.3	P1
ING1	ENST00000375774.3	c.1076A>G	p.Asn359Ser	missense_variant	2/2	1
ING1	ENST00000338450.7	c.515A>G	p.Asn172Ser	missense_variant	2/2	1
ING1	ENST00000375775.4	c.440A>G	p.Asn147Ser	missense_variant	2/2	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Squamous cell carcinoma of the head and neck Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 15, 2000

- -

Computational scores

Source: dbNSFP v4.3

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;T;T;T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.45	T;T;T;T
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.9	D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Benign	0.14	T;T;T;D
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

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: rs121909251; hg19: chr13-111372086;