chrX-103253803-C-G

Variant names:

• chrX-103253803-C-G
• NM_153333.3:c.177G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/21 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
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12142834).

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.177G>C	p.Gln59His	missense	Exon 3 of 3	NP_699164.1	Q8IYN2
	TCEAL8	NM_001006684.2		c.177G>C	p.Gln59His	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.177G>C	p.Gln59His	missense	Exon 3 of 3	ENSP00000361770.3	Q8IYN2
	TCEAL8	ENST00000360000.8	TSL:1	c.177G>C	p.Gln59His	missense	Exon 2 of 2	ENSP00000353093.4	Q8IYN2
	TCEAL8	ENST00000866567.1		c.177G>C	p.Gln59His	missense	Exon 3 of 3	ENSP00000536626.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.56
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.047
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.53	P
Vest4		0.22
MutPred		0.42		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
Mutation Taster		=100/0	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

hg19: chrX-102508731;