Variant X-89922686-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138960.4(TGIF2LX):c.601T>A(p.Ser201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,098,254 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000015 ( 0 hom. 5 hem. )

Failed GnomAD Quality Control

Consequence

TGIF2LX
NM_138960.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.623

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035106927).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGIF2LX	NM_138960.4 linkuse as main transcript	c.601T>A	p.Ser201Thr	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.601T>A	p.Ser201Thr	missense_variant	2/2	1	NM_138960.4	ENSP00000355119.4		Q8IUE1
TGIF2LX	ENST00000561129.2 linkuse as main transcript	c.601T>A	p.Ser201Thr	missense_variant	1/1	6		ENSP00000453704.1		Q8IUE1

Frequencies

GnomAD3 genomes

AF:

0.0000355

AC:

AN:

112705

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34859

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183252

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000535

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1098254

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363610

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000671

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000355

AC:

AN:

112705

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34859

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00150

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000264

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

Aug 21, 2023

The c.601T>A (p.S201T) alteration is located in exon 2 (coding exon 1) of the TGIF2LX gene. This alteration results from a T to A substitution at nucleotide position 601, causing the serine (S) at amino acid position 201 to be replaced by a threonine (T). 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

0.076

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.7

DANN

Benign

0.11

DEOGEN2

Benign

0.0031

T;T

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.30

.;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.033

Sift

Benign

0.70

T;T

Sift4G

Benign

0.36

T;T

Polyphen

0.0060

B;B

Vest4

0.048

MutPred

0.13

Loss of phosphorylation at S201 (P = 0.0528);Loss of phosphorylation at S201 (P = 0.0528);

MVP

0.36

MPC

0.83

ClinPred

0.015

GERP RS

1.6

Varity_R

0.059

gMVP

0.058

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