X-103609152-T-G

Variant names:

• chrX-103609152-T-G
• rs1333760621
• NM_032926.3:c.88T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_032926.3(TCEAL3):​c.88T>G​(p.Ser30Ala) 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. 14/20 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: TCEAL3 NM_032926.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.113

Genes affected

TCEAL3 (HGNC:28247): (transcription elongation factor A like 3) 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.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity TCAL3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041156054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL3	NM_032926.3	c.88T>G	p.Ser30Ala	missense_variant	Exon 3 of 3	ENST00000372627.10	NP_116315.1
TCEAL3	NM_001006933.2	c.88T>G	p.Ser30Ala	missense_variant	Exon 3 of 3		NP_001006934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL3	ENST00000372627.10	c.88T>G	p.Ser30Ala	missense_variant	Exon 3 of 3	1	NM_032926.3	ENSP00000361710.5
TCEAL3	ENST00000243286.7	c.88T>G	p.Ser30Ala	missense_variant	Exon 3 of 3	1		ENSP00000243286.3
TCEAL3	ENST00000372628.5	c.88T>G	p.Ser30Ala	missense_variant	Exon 3 of 3	5		ENSP00000361711.1
TCEAL3	ENST00000477014.1	n.158+479T>G		intron_variant	Intron 2 of 6	5

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

Aug 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88T>G (p.S30A) alteration is located in exon 3 (coding exon 1) of the TCEAL3 gene. This alteration results from a T to G substitution at nucleotide position 88, causing the serine (S) at amino acid position 30 to be replaced by an alanine (A). 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	0.077
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.20
DEOGEN2	Benign	0.017	T;T;T
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.43	.;T;.
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Benign	0.011
Sift	Benign	0.52	T;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.12
MutPred		0.37		Loss of phosphorylation at S30 (P = 6e-04);Loss of phosphorylation at S30 (P = 6e-04);Loss of phosphorylation at S30 (P = 6e-04);
MVP		0.30
MPC		0.73
ClinPred		0.044	T
GERP RS		2.8
Varity_R		0.081
gMVP		0.0060

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: rs1333760621; hg19: chrX-102864080;