Variant X-89922177-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138960.4(TGIF2LX):c.92C>T(p.Ser31Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,097,688 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

TGIF2LX
NM_138960.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.13026601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGIF2LX	NM_138960.4 link	c.92C>T	p.Ser31Leu	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 link	c.92C>T	p.Ser31Leu	missense_variant	2/2	1	NM_138960.4	ENSP00000355119.4		Q8IUE1
TGIF2LX	ENST00000561129.2 link	c.92C>T	p.Ser31Leu	missense_variant	1/1	6		ENSP00000453704.1		Q8IUE1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181145

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66461

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

1097688

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000713

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Oct 03, 2023

The c.92C>T (p.S31L) 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 92, causing the serine (S) at amino acid position 31 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.68

.;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.057

T;T

Polyphen

0.91

P;P

Vest4

0.16

MutPred

0.26

Loss of glycosylation at S31 (P = 0.0224);Loss of glycosylation at S31 (P = 0.0224);

MVP

0.093

MPC

1.8

ClinPred

0.48

GERP RS

1.4

Varity_R

0.11

gMVP

0.46

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over