X-103253803-C-G

Position:

• chrX-103253803-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153333.3(TCEAL8):​c.177G>C​(p.Gln59His) 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. 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: 23)
• Consequence: TCEAL8 NM_153333.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.555

Genes affected

TCEAL8 (HGNC:28683): (transcription elongation factor A like 8) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family contain TFA domains and may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.12142834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL8	NM_153333.3	c.177G>C	p.Gln59His	missense_variant	3/3	ENST00000372685.8	NP_699164.1
TCEAL8	NM_001006684.2	c.177G>C	p.Gln59His	missense_variant	2/2		NP_001006685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL8	ENST00000372685.8	c.177G>C	p.Gln59His	missense_variant	3/3	1	NM_153333.3	ENSP00000361770	P1
TCEAL8	ENST00000360000.8	c.177G>C	p.Gln59His	missense_variant	2/2	1		ENSP00000353093	P1
TCEAL8	ENST00000451678.1	c.91-13G>C		splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000390880

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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

Jan 31, 2024

The c.177G>C (p.Q59H) alteration is located in exon 3 (coding exon 1) of the TCEAL8 gene. This alteration results from a G to C substitution at nucleotide position 177, causing the glutamine (Q) at amino acid position 59 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T;T
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.25	.;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.047
Sift	Benign	0.11	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.53	P;P
Vest4		0.22
MutPred		0.42		Gain of catalytic residue at Q59 (P = 0.0426);Gain of catalytic residue at Q59 (P = 0.0426);
MVP		0.014
MPC		0.38
ClinPred		0.32	T
GERP RS		-0.40
Varity_R		0.077
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-102508731;