chr22-41436568-A-T

Variant names:

• chr22-41436568-A-T
• rs1202482530
• NM_016272.4:c.778T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016272.4(TOB2):​c.778T>A​(p.Phe260Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F260V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOB2 NM_016272.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.89
• Publications: 0 publications found

Genes affected

TOB2 (HGNC:11980): (transducer of ERBB2, 2) TOB2 belongs to the TOB (see TOB1; MIM 605523)/BTG1 (MIM 109580) family of antiproliferative proteins, which are involved in the regulation of cell cycle progression.[supplied by OMIM, Apr 2004]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016272.4. 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
	TOB2	NM_016272.4	MANE Select	c.778T>A	p.Phe260Ile	missense	Exon 2 of 2	NP_057356.1	Q14106-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOB2	ENST00000327492.4	TSL:1 MANE Select	c.778T>A	p.Phe260Ile	missense	Exon 2 of 2	ENSP00000331305.3	Q14106-1
	TOB2	ENST00000434408.2	TSL:2	c.778T>A	p.Phe260Ile	missense	Exon 2 of 2	ENSP00000388549.2	Q14106-1
	TOB2	ENST00000901391.1		c.778T>A	p.Phe260Ile	missense	Exon 2 of 2	ENSP00000571450.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.061	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.79		Gain of sheet (P = 0.039)
MVP		0.35
MPC		1.3
ClinPred		0.97	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.46
gMVP		0.67
Mutation Taster		=47/53	disease causing

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: rs1202482530; hg19: chr22-41832572;