NM_021809.7:c.337G>A

Variant names:

• chr20-36591054-G-A
• rs151198555
• NM_021809.7:c.337G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021809.7(TGIF2):​c.337G>A​(p.Val113Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,602,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: TGIF2 NM_021809.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023867369).

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.337G>A	p.Val113Met	missense	Exon 3 of 3	NP_068581.1	Q9GZN2-1
	TGIF2	NM_001199513.2		c.337G>A	p.Val113Met	missense	Exon 3 of 3	NP_001186442.1	Q9GZN2-1
	TGIF2	NM_001199514.2		c.337G>A	p.Val113Met	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.337G>A	p.Val113Met	missense	Exon 3 of 3	ENSP00000362979.3	Q9GZN2-1
	TGIF2-RAB5IF	ENST00000558530.1	TSL:3	c.192+12088G>A		intron	N/A	ENSP00000454021.1
	TGIF2	ENST00000373874.6	TSL:2	c.337G>A	p.Val113Met	missense	Exon 3 of 3	ENSP00000362981.2	Q9GZN2-1

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000129 AC: 32 AN: 247428 AF XY: 0.000142

Gnomad AFR exome AF: 0.000741

Gnomad AMR exome AF: 0.0000879

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000143

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000219 AC: 318 AN: 1450100 Hom.: 0 Cov.: 31 AF XY: 0.000218 AC XY: 157 AN XY: 719114

African (AFR) AF: 0.00102 AC: 34 AN: 33272

American (AMR) AF: 0.0000905 AC: 4 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25750

East Asian (EAS) AF: 0.00 AC: 0 AN: 39350

South Asian (SAS) AF: 0.00 AC: 0 AN: 85574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.000229 AC: 253 AN: 1103224

Other (OTH) AF: 0.000452 AC: 27 AN: 59788

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74432

African (AFR) AF: 0.000602 AC: 25 AN: 41544

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000377 Hom.: 0

Bravo AF: 0.000287

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000124 AC: 15

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	Benign	0.082
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.028
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		0.024	B
Vest4		0.065
MVP		0.58
MPC		0.43
ClinPred		0.0040	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.020
gMVP		0.56
Mutation Taster		=85/15	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

Other links and lift over

dbSNP: rs151198555; hg19: chr20-35219457;