X-103253819-G-A

Position:

• chrX-103253819-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_153333.3(TCEAL8):​c.161C>T​(p.Pro54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000819 in 1,098,248 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000082 (0 hom. 3 hem.)
• Consequence: TCEAL8 NM_153333.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.08

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05415404).
• BP6: Variant X-103253819-G-A is Benign according to our data. Variant chrX-103253819-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3175065.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEAL8	NM_153333.3	c.161C>T	p.Pro54Leu	missense_variant	3/3	ENST00000372685.8	NP_699164.1
TCEAL8	NM_001006684.2	c.161C>T	p.Pro54Leu	missense_variant	2/2		NP_001006685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEAL8	ENST00000372685.8	c.161C>T	p.Pro54Leu	missense_variant	3/3	1	NM_153333.3	ENSP00000361770	P1
TCEAL8	ENST00000360000.8	c.161C>T	p.Pro54Leu	missense_variant	2/2	1		ENSP00000353093	P1
TCEAL8	ENST00000451678.1	c.91-29C>T		intron_variant		3		ENSP00000390880

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000819 AC: 9 AN: 1098248 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3 AN XY: 363602

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000831

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	9.3
DANN	Benign	0.71
DEOGEN2	Benign	0.0017	T;T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.94	N;N
MutationTaster	Benign	0.56	D;D
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.8	N;N
REVEL	Benign	0.068
Sift	Benign	1.0	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0	B;B
Vest4		0.16
MutPred		0.41		Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);
MVP		0.16
MPC		0.41
ClinPred		0.060	T
GERP RS		2.5
Varity_R		0.027
gMVP		0.41

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

Other links and lift over

dbSNP: rs1925165714; hg19: chrX-102508747;