20-36591351-A-C

Variant names:

• chr20-36591351-A-C
• NM_021809.7:c.634A>C
• TGIF2 p.Met212Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021809.7(TGIF2):​c.634A>C​(p.Met212Leu) 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. 16/22 in silico tools predict a benign 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. M212V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGIF2 NM_021809.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07564026).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021809.7. 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
	TGIF2	NM_021809.7	MANE Select	c.634A>C	p.Met212Leu	missense	Exon 3 of 3	NP_068581.1	Q9GZN2-1
	TGIF2	NM_001199513.2		c.634A>C	p.Met212Leu	missense	Exon 3 of 3	NP_001186442.1	Q9GZN2-1
	TGIF2	NM_001199514.2		c.634A>C	p.Met212Leu	missense	Exon 3 of 3	NP_001186443.1	Q9GZN2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGIF2	ENST00000373872.9	TSL:1 MANE Select	c.634A>C	p.Met212Leu	missense	Exon 3 of 3	ENSP00000362979.3	Q9GZN2-1
	TGIF2-RAB5IF	ENST00000558530.1	TSL:3	c.192+12385A>C		intron	N/A	ENSP00000454021.1
	TGIF2	ENST00000373874.6	TSL:2	c.634A>C	p.Met212Leu	missense	Exon 3 of 3	ENSP00000362981.2	Q9GZN2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Benign	0.84
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.72	N
PhyloP100		2.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.18
Mutation Taster		=79/21	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-35219754;