chr17-50863450-T-A

Variant names:

• chr17-50863450-T-A
• NM_005749.4:c.568A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005749.4(TOB1):​c.568A>T​(p.Thr190Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TOB1 NM_005749.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

Genes affected

TOB1 (HGNC:11979): (transducer of ERBB2, 1) This gene encodes a member of the transducer of erbB-2 /B-cell translocation gene protein family. Members of this family are anti-proliferative factors that have the potential to regulate cell growth. The encoded protein may function as a tumor suppressor. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005749.4. 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
	TOB1	NM_005749.4	MANE Select	c.568A>T	p.Thr190Ser	missense	Exon 2 of 2	NP_005740.1	P50616
	TOB1	NM_001243877.2		c.568A>T	p.Thr190Ser	missense	Exon 3 of 3	NP_001230806.1	P50616
	TOB1	NM_001243885.2		c.151A>T	p.Thr51Ser	missense	Exon 2 of 2	NP_001230814.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOB1	ENST00000499247.3	TSL:1 MANE Select	c.568A>T	p.Thr190Ser	missense	Exon 2 of 2	ENSP00000427695.1	P50616
	TOB1	ENST00000268957.3	TSL:1	c.568A>T	p.Thr190Ser	missense	Exon 3 of 3	ENSP00000268957.3	P50616
	TOB1	ENST00000851192.1		c.568A>T	p.Thr190Ser	missense	Exon 2 of 2	ENSP00000521251.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 31

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	0.98
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.048	D
Polyphen		0.99	D
Vest4		0.65
MutPred		0.18		Loss of glycosylation at S189 (P = 0.0781)
MVP		0.30
MPC		0.97
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.76
gMVP		0.58

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

hg19: chr17-48940811;