X-103253788-G-T

Variant names:

• chrX-103253788-G-T
• rs751665843
• NM_153333.3:c.192C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153333.3(TCEAL8):​c.192C>A​(p.Asp64Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: TCEAL8 NM_153333.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153333.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL8	NM_153333.3	MANE Select	c.192C>A	p.Asp64Glu	missense	Exon 3 of 3	NP_699164.1	Q8IYN2
	TCEAL8	NM_001006684.2		c.192C>A	p.Asp64Glu	missense	Exon 2 of 2	NP_001006685.1	Q8IYN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL8	ENST00000372685.8	TSL:1 MANE Select	c.192C>A	p.Asp64Glu	missense	Exon 3 of 3	ENSP00000361770.3	Q8IYN2
	TCEAL8	ENST00000360000.8	TSL:1	c.192C>A	p.Asp64Glu	missense	Exon 2 of 2	ENSP00000353093.4	Q8IYN2
	TCEAL8	ENST00000866567.1		c.192C>A	p.Asp64Glu	missense	Exon 3 of 3	ENSP00000536626.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0093	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		1.4
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.15
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.64	P
Vest4		0.42
MutPred		0.73		Gain of glycosylation at K62 (P = 0.1494)
MVP		0.067
MPC		0.95
ClinPred		0.96	D
GERP RS		2.7
Varity_R		0.18
gMVP		0.46
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs751665843; hg19: chrX-102508716;