X-103274139-C-T

Variant names:

• chrX-103274139-C-T
• rs748439533
• NM_001012979.3:c.425G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001012979.3(TCEAL5):​c.425G>A​(p.Ser142Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,210,392 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 2 hem.)
• Consequence: TCEAL5 NM_001012979.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0160
• Publications: 1 publications found

Genes affected

TCEAL5 (HGNC:22282): (transcription elongation factor A like 5) This gene, which is located on the X chromosome, encodes a protein which contains a BEX (brain expressed X-liked like family) domain. This domain is found in proteins encoded by the TCEAL elongation factor (transcription elongation factor A (SII)-like) gene family also located on the X chromosome. The coding region for this gene is located entirely in the terminal exon. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.063521385).
• BS2: High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL5	NM_001012979.3	c.425G>A	p.Ser142Asn	missense_variant	Exon 3 of 3	ENST00000372680.2	NP_001012997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL5	ENST00000372680.2	c.425G>A	p.Ser142Asn	missense_variant	Exon 3 of 3	1	NM_001012979.3	ENSP00000361765.1

Frequencies

GnomAD3 genomes AF: 0.0000803 AC: 9 AN: 112145 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000163 AC: 3 AN: 183516 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000127 AC: 14 AN: 1098247 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2 AN XY: 363607

African (AFR) AF: 0.000455 AC: 12 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54147

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842148

Other (OTH) AF: 0.0000434 AC: 2 AN: 46091

GnomAD4 genome AF: 0.0000803 AC: 9 AN: 112145 Hom.: 0 Cov.: 23 AF XY: 0.000146 AC XY: 5 AN XY: 34293

African (AFR) AF: 0.000292 AC: 9 AN: 30805

American (AMR) AF: 0.00 AC: 0 AN: 10651

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3568

South Asian (SAS) AF: 0.00 AC: 0 AN: 2688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53232

Other (OTH) AF: 0.00 AC: 0 AN: 1523

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.425G>A (p.S142N) alteration is located in exon 3 (coding exon 1) of the TCEAL5 gene. This alteration results from a G to A substitution at nucleotide position 425, causing the serine (S) at amino acid position 142 to be replaced by an asparagine (N). 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	0.18
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.95
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.0010	T
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.016
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.073
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.98	D
Vest4		0.17
MVP		0.28
MPC		0.85
ClinPred		0.083	T
GERP RS		1.9
Varity_R		0.066
gMVP		0.018
Mutation Taster		=99/1	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: rs748439533; hg19: chrX-102529067;