20-36591177-C-T

Position:

• chr20-36591177-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021809.7(TGIF2):​c.460C>T​(p.Pro154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGIF2 NM_021809.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

Genes affected

TGIF2 (HGNC:15764): (TGFB induced factor homeobox 2) The protein encoded by this gene is a DNA-binding homeobox protein and a transcriptional repressor, which appears to repress transcription by recruiting histone deacetylases to TGF beta-responsive genes. This gene is amplified and over-expressed in some ovarian cancers. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 1. Read-through transcription also exists between this gene and the neighboring downstream C20orf24 (chromosome 20 open reading frame 24) gene. [provided by RefSeq, Dec 2010]

TGIF2-RAB5IF (HGNC:44664): (TGIF2-RAB5IF readthrough) This locus represents naturally occurring read-through transcription between the neighboring TGIF2 (TGFB-induced factor homeobox 2) and C20orf24 (chromosome 20 open reading frame 24) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11465579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGIF2	NM_021809.7	c.460C>T	p.Pro154Ser	missense_variant	3/3	ENST00000373872.9	NP_068581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGIF2	ENST00000373872.9	c.460C>T	p.Pro154Ser	missense_variant	3/3	1	NM_021809.7	ENSP00000362979.3
TGIF2-RAB5IF	ENST00000558530.1	c.192+12211C>T		intron_variant		3		ENSP00000454021.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2023

The c.460C>T (p.P154S) alteration is located in exon 3 (coding exon 2) of the TGIF2 gene. This alteration results from a C to T substitution at nucleotide position 460, causing the proline (P) at amino acid position 154 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T;T;T;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.65	.;.;T;T;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L;L;.;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.3	N;N;N;.;N
REVEL	Benign	0.050
Sift	Uncertain	0.023	D;D;D;.;D
Sift4G	Benign	0.32	T;T;T;T;T
Polyphen		0.010	B;B;.;B;B
Vest4		0.040
MutPred		0.19		Gain of phosphorylation at P154 (P = 0.0339);Gain of phosphorylation at P154 (P = 0.0339);Gain of phosphorylation at P154 (P = 0.0339);Gain of phosphorylation at P154 (P = 0.0339);Gain of phosphorylation at P154 (P = 0.0339);
MVP		0.67
MPC		0.43
ClinPred		0.057	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.020
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-35219580;