Variant X-89922683-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138960.4(TGIF2LX):c.598C>T(p.Pro200Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

TGIF2LX
NM_138960.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.568

Variant links:

Genes affected

TGIF2LX (HGNC:18570): (TGFB induced factor homeobox 2 like X-linked) This gene encodes a member of the TALE/TGIF homeobox family of transcription factors. Testis-specific expression suggests that this gene may play a role in spermatogenesis. A homolog of this gene lies within the male specific region of chromosome Y, in a block of sequence that is thought to be the result of a large X-to-Y transposition. [provided by RefSeq, Jul 2008]

TGIF2LX links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066664994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGIF2LX	NM_138960.4 linkuse as main transcript	c.598C>T	p.Pro200Ser	missense_variant	2/2	ENST00000283891.6	NP_620410.3	Q8IUE1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGIF2LX	ENST00000283891.6 linkuse as main transcript	c.598C>T	p.Pro200Ser	missense_variant	2/2	1	NM_138960.4	ENSP00000355119.4		Q8IUE1
TGIF2LX	ENST00000561129.2 linkuse as main transcript	c.598C>T	p.Pro200Ser	missense_variant	1/1	6		ENSP00000453704.1		Q8IUE1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000273

AC:

AN:

1098249

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363605

show subpopulations

Gnomad4 AFR exome

AF:

0.0000757

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.598C>T (p.P200S) alteration is located in exon 2 (coding exon 1) of the TGIF2LX gene. This alteration results from a C to T substitution at nucleotide position 598, causing the proline (P) at amino acid position 200 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

0.073

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.089

DANN

Benign

0.37

DEOGEN2

Benign

0.0086

T;T

FATHMM_MKL

Benign

0.00061

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.064

Sift

Benign

0.18

T;T

Sift4G

Benign

0.089

T;T

Polyphen

0.0010

B;B

Vest4

0.072

MutPred

0.28

Gain of phosphorylation at P200 (P = 0.0075);Gain of phosphorylation at P200 (P = 0.0075);

MVP

0.17

MPC

0.85

ClinPred

0.096

GERP RS

-5.3

Varity_R

0.044

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over