X-103274530-G-A

Variant names:

• chrX-103274530-G-A
• rs141706642
• NM_001012979.3:c.34C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001012979.3(TCEAL5):​c.34C>T​(p.Pro12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,199,574 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.0000092 (0 hom. 0 hem.)
• Consequence: TCEAL5 NM_001012979.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10

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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09160879).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL5	NM_001012979.3	c.34C>T	p.Pro12Ser	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.34C>T	p.Pro12Ser	missense_variant	Exon 3 of 3	1	NM_001012979.3	ENSP00000361765.1

Frequencies

GnomAD3 genomes AF: 0.0000630 AC: 7 AN: 111057 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000954

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000352 AC: 6 AN: 170558 AF XY: 0.00

Gnomad AFR exome AF: 0.000463

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: 0.00000919 AC: 10 AN: 1088517 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 356603

African (AFR) AF: 0.000351 AC: 9 AN: 25674

American (AMR) AF: 0.00 AC: 0 AN: 33334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18823

East Asian (EAS) AF: 0.00 AC: 0 AN: 30142

South Asian (SAS) AF: 0.00 AC: 0 AN: 51626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4086

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 838957

Other (OTH) AF: 0.0000219 AC: 1 AN: 45615

GnomAD4 genome AF: 0.0000630 AC: 7 AN: 111057 Hom.: 0 Cov.: 22 AF XY: 0.0000600 AC XY: 2 AN XY: 33353

African (AFR) AF: 0.000164 AC: 5 AN: 30420

American (AMR) AF: 0.0000954 AC: 1 AN: 10487

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.00 AC: 0 AN: 2596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5971

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52969

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.0000839 Hom.: 0

Bravo AF: 0.000151

ExAC AF: 0.0000494 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.34C>T (p.P12S) alteration is located in exon 3 (coding exon 1) of the TCEAL5 gene. This alteration results from a C to T substitution at nucleotide position 34, causing the proline (P) at amino acid position 12 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	0.13
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.1
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.13
Sift	Uncertain	0.021	D
Sift4G	Benign	0.45	T
Polyphen		0.98	D
Vest4		0.12
MVP		0.33
MPC		0.67
ClinPred		0.15	T
GERP RS		3.3
Varity_R		0.22
gMVP		0.021
Mutation Taster		=98/2	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

Publications

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Other links and lift over

dbSNP: rs141706642; hg19: chrX-102529458;