X-89922431-C-G

Position:

• chrX-89922431-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000283891.6(TGIF2LX):​c.346C>G​(p.Arg116Gly) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TGIF2LX ENST00000283891.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.865

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]

ACMG classification

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=0.054549575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGIF2LX	NM_138960.4	c.346C>G	p.Arg116Gly	missense_variant	2/2	ENST00000283891.6	NP_620410.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGIF2LX	ENST00000283891.6	c.346C>G	p.Arg116Gly	missense_variant	2/2	1	NM_138960.4	ENSP00000355119	P1
TGIF2LX	ENST00000561129.2	c.346C>G	p.Arg116Gly	missense_variant	1/1			ENSP00000453704	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.346C>G (p.R116G) alteration is located in exon 2 (coding exon 1) of the TGIF2LX gene. This alteration results from a C to G substitution at nucleotide position 346, causing the arginine (R) at amino acid position 116 to be replaced by a glycine (G). 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	0.082
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.50
DEOGEN2	Benign	0.0036	T;T
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.20	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.19	N;N
REVEL	Benign	0.18
Sift	Benign	0.049	D;D
Sift4G	Uncertain	0.052	T;T
Polyphen		0.0030	B;B
Vest4		0.065
MutPred		0.39		Loss of MoRF binding (P = 0.0616);Loss of MoRF binding (P = 0.0616);
MVP		0.068
MPC		1.1
ClinPred		0.072	T
GERP RS		-1.3
Varity_R		0.052
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chrX-89177430;