X-102126903-C-T

Variant names:

• chrX-102126903-C-T
• rs149647049
• NM_080390.4:c.73C>T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_080390.4(TCEAL2):​c.73C>T​(p.Pro25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,210,321 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 384 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., 16 hem., cov: 23)
  • Exomes 𝑓: 0.00095 (0 hom. 368 hem.)
• Consequence: TCEAL2 NM_080390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.954

Genes affected

TCEAL2 (HGNC:29818): (transcription elongation factor A like 2) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005600959).
• BS2: High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL2	NM_080390.4	c.73C>T	p.Pro25Ser	missense_variant	Exon 3 of 3	ENST00000372780.6	NP_525129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL2	ENST00000372780.6	c.73C>T	p.Pro25Ser	missense_variant	Exon 3 of 3	1	NM_080390.4	ENSP00000361866.1
TCEAL2	ENST00000329035.2	c.73C>T	p.Pro25Ser	missense_variant	Exon 3 of 3	5		ENSP00000332359.2
TCEAL2	ENST00000651085.1	n.153+458C>T		intron_variant	Intron 2 of 3
TCEAL2	ENST00000476749.1	n.*3C>T		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.000766 AC: 86 AN: 112318 Hom.: 0 Cov.: 23 AF XY: 0.000463 AC XY: 16 AN XY: 34524

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000942

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000365

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.000660

GnomAD3 exomes AF: 0.00100 AC: 184 AN: 183215 Hom.: 0 AF XY: 0.000931 AC XY: 63 AN XY: 67665

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.00106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000579

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00156

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.000952 AC: 1045 AN: 1097948 Hom.: 0 Cov.: 31 AF XY: 0.00101 AC XY: 368 AN XY: 363332

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.000258

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.0000493

Gnomad4 NFE exome AF: 0.00110

Gnomad4 OTH exome AF: 0.000651

GnomAD4 genome AF: 0.000765 AC: 86 AN: 112373 Hom.: 0 Cov.: 23 AF XY: 0.000463 AC XY: 16 AN XY: 34589

Gnomad4 AFR AF: 0.000129

Gnomad4 AMR AF: 0.0000941

Gnomad4 ASJ AF: 0.00113

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000366

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.000651

Alfa AF: 0.00131 Hom.: 29

Bravo AF: 0.000793

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.00119 AC: 8

ExAC AF: 0.00107 AC: 130

EpiCase AF: 0.00240

EpiControl AF: 0.00202

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.73C>T (p.P25S) alteration is located in exon 3 (coding exon 1) of the TCEAL2 gene. This alteration results from a C to T substitution at nucleotide position 73, causing the proline (P) at amino acid position 25 to be replaced by a serine (S). 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	0.072
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	10
DANN	Benign	0.85
DEOGEN2	Benign	0.0030	T;T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.44	T;.
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.0056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.0030
Sift	Benign	0.096	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.0070	B;B
Vest4		0.057
MVP		0.068
MPC		0.32
ClinPred		0.0087	T
GERP RS		0.55
Varity_R		0.034
gMVP		0.012

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: rs149647049; hg19: chrX-101381875; COSMIC: COSV100216195; COSMIC: COSV100216195;